Affinage

CCR7

C-C chemokine receptor type 7 · UniProt P32248

Length
378 aa
Mass
42.9 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCR7 is a Gαi-coupled seven-transmembrane chemokine receptor that drives directional and collective migration of dendritic cells and lymphocytes into and within secondary lymphoid organs in response to its ligands CCL19 (ELC) and CCL21 (SLC) (PMID:9153236, PMID:9498785, PMID:15308107). Ligand engagement triggers calcium mobilization, actin polymerization, and chemotaxis that are abolished by pertussis toxin, establishing Gαi-dependence (PMID:9153236, PMID:9498785), and the receptor is sharply upregulated on dendritic cells during maturation to license their migration toward CCL19/CCL21 (PMID:9743376). Signaling outputs are partitioned across distinct C-terminal motifs and largely independent downstream modules: a Ser/Thr tail motif controls ERK1/2 activation while the full C-terminus is required for G-protein coupling, with internalization occurring independently of G-protein coupling (PMID:18664492), and PI3K/Akt, MAPK, and RhoA modules separately govern DC survival, chemotaxis, and actin dynamics (PMID:32351499). Polarization and migration require ROCK, the actin-bundling protein L-plastin, and Jak3 (PMID:12729902, PMID:20194718, PMID:19759904), and CCR7 nucleates an endomembrane signaling complex in which β-arrestin- and Src-dependent trafficking leads to Src phosphorylation of CCR7, Vav1 recruitment, and local Rac1 activation that generates leading-edge lamellipodia (PMID:31644919). Receptor behavior is tuned by constitutive ubiquitylation enabling post-endocytic recycling through the trans-Golgi network (PMID:22797918), by N-glycosylation and tyrosine sulfation that modulate ligand sensitivity and endocytosis (PMID:26819318, PMID:28841151), and by homodimerization/oligomerization that is itself supported by glycolytic metabolism (PMID:28819198, PMID:29941886). Beyond steering individual cells, CCR7 acts as a chemokine sink, internalizing CCL19 to self-generate and sharpen gradients for long-range collective DC guidance (PMID:37656776). CCR7 governs key positional decisions in immunity: dendritic cell entry into lymphatics and lymph nodes (PMID:15308107), intrathymic progenitor positioning and T cell development (PMID:15302903), T cell egress from peripheral tissue into afferent lymph (PMID:16116469), lymph node egress via a CCL19→ERK5→KLF2→S1PR1 axis (PMID:22334704), Treg localization and homeostasis (PMID:24378538), and neutrophil clearance into draining lymph nodes (PMID:35119939). CCR7 also functions as a pro-tumoral and survival signal in cancer, driving invasion via a HIF-1α and Sp1/heparanase program and PI3Kγ-dependent survival in lymphoma (PMID:23649655, PMID:17178876, PMID:37379367).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 Medium

    Established a transcriptional input to CCR7 expression before its ligand or function was known, linking the orphan receptor BLR2/EBI1 to viral B cell transformation programs.

    Evidence Estrogen-inducible EBNA2 expression in EBV-negative BL41 cells with Northern/RT-PCR

    PMID:7488016

    Open questions at the time
    • Does not define the receptor's ligand or signaling function
    • Single inducible system, no direct promoter occupancy shown
  2. 1997 High

    Deorphanized CCR7 by identifying CCL19 (ELC) as a specific high-affinity functional ligand, converting an orphan receptor into a defined chemotactic receptor.

    Evidence Alkaline phosphatase fusion binding, calcium flux, and chemotaxis in transfected cells

    PMID:9153236

    Open questions at the time
    • Did not yet identify CCL21 as a second ligand
    • G-protein coupling not yet dissected
  3. 1998 High

    Defined the transducer class by showing CCR7 signals through Gαi and is induced upon DC maturation, connecting receptor biochemistry to a physiological cell state.

    Evidence Pertussis toxin inhibition of chemotaxis/actin polymerization; flow cytometry and functional assays in maturing DCs

    PMID:9498785 PMID:9743376

    Open questions at the time
    • Downstream effectors beyond Gαi not identified
    • Mechanism of maturation-induced upregulation not defined
  4. 2003 Medium

    Began dissecting downstream effectors, placing Rho kinase but not ERK2 in the polarization/chemotaxis pathway.

    Evidence Y-27632 and ERK inhibitor treatment with polarization/chemotaxis readouts in T cells

    PMID:12729902

    Open questions at the time
    • Pharmacological only, no genetic confirmation
    • Does not map the GEF or GTPase linking CCR7 to ROCK
  5. 2004 High

    Established the in vivo physiological role of CCR7 in DC entry into lymphatics/lymph nodes and intrathymic progenitor positioning, moving from cell-based assays to organismal immunology.

    Evidence CCR7-deficient mice, immunohistology, flow cytometry, mixed bone marrow chimeras

    PMID:15302903 PMID:15308107

    Open questions at the time
    • Does not resolve the molecular signaling required for these positioning events
    • Ligand contributions (CCL19 vs CCL21) not separated
  6. 2005 High

    Extended CCR7 function to retrograde T cell egress from peripheral tissue into afferent lymph, defining a molecular basis for tissue exit.

    Evidence Adoptive transfer of CCR7+ vs CCR7- effector T cells in asthmatic lung

    PMID:16116469

    Open questions at the time
    • Signaling downstream of CCR7 in this context not defined
    • Single tissue/disease model
  7. 2006 Medium

    Linked CCR7 to tumor biology by showing endothelin/HIF-1α-driven CCR7 induction promotes invasion, framing CCR7 as a hijacked metastatic effector.

    Evidence Dominant-negative HIF-1α, CCR7-neutralizing antibody, invasion assays in breast tumor cells

    PMID:17178876

    Open questions at the time
    • Single cancer cell context
    • Does not establish in vivo metastatic requirement
  8. 2007 Medium

    Demonstrated context-specific antigen-presenting cell trafficking via CCL21 and uncovered an unexpected anti-proliferative function of CCR7 signaling.

    Evidence Corneal APC tracking with anti-CCL21 neutralization; CCR7-/- T cell proliferation with p27Kip1/CDK1 Western blots

    PMID:17515886 PMID:17982037

    Open questions at the time
    • Mechanism coupling CCR7 to cell-cycle machinery not fully mapped
    • Single-lab studies
  9. 2008 High

    Defined the structure-function logic of the CCR7 C-terminus and showed ligand occupancy in lymphoid organs continuously desensitizes the receptor in vivo.

    Evidence C-terminal deletion/coupling-dead mutants with multiple functional assays; in vivo occupancy in Ccl19-/- and plt/plt mice

    PMID:18664492 PMID:19017956

    Open questions at the time
    • Internalization machinery (adaptors, kinases) not identified at this stage
    • Resensitization mechanism in vivo not resolved
  10. 2009 Medium

    Identified Jak3 as a required effector for CCR7-driven DC migration, expanding the downstream effector network beyond classical GPCR components.

    Evidence Jak3-/- mice with in vitro/in vivo DC chemotaxis and MLR assays

    PMID:19759904

    Open questions at the time
    • Biochemical link between CCR7 and Jak3 not established
    • Single lab
  11. 2010 High

    Separated proximal CCR7 signaling from cytoskeletal polarization by showing L-plastin is required for receptor polarization and migration but not F-actin polymerization.

    Evidence LPL-/- mice, two-photon imaging, CCR7 localization, chemotaxis and thymic egress assays

    PMID:20194718

    Open questions at the time
    • How CCR7 signaling activates L-plastin not defined
    • Connection to ROCK/RhoA modules unresolved
  12. 2012 High

    Revealed receptor trafficking control: constitutive ubiquitylation enables TGN-mediated recycling, and an egress signaling axis (ERK5→KLF2→S1PR1) was placed downstream of CCR7.

    Evidence Ubiquitylation-deficient mutant trafficking assays; ERK5 conditional knockout with migration assays

    PMID:22334704 PMID:22797918

    Open questions at the time
    • The ubiquitin ligase acting on CCR7 not identified
    • ERK5 axis tested in limited cell models
  13. 2013 High

    Connected CCR7-dependent localization to homeostatic function, showing CCR7 positions Tregs in IL-2-rich T cell zones to maintain a specific Treg subset.

    Evidence CCR7 reporter/KO mice, in vivo IL-2 and ICOS blockade, flow cytometry

    PMID:24378538

    Open questions at the time
    • Does not address CCR7 signaling intermediates in Tregs
    • Tissue-specific ligand sources not mapped
  14. 2014 Medium

    Established epigenetic and transcriptional control of CCR7 expression that determines which DC subsets can migrate to lymph nodes.

    Evidence ChIP for H3K27me3 at Ccr7 in DC subsets; FOXO1 promoter ChIP and genetic rescue (reported 2015)

    PMID:25297875 PMID:25786691

    Open questions at the time
    • Upstream signals controlling these marks/FOXO1 activity not defined
    • Single-lab ChIP studies
  15. 2016 High

    Showed post-translational glycosylation tunes CCR7 ligand sensitivity and endocytosis, and that CCR7 restricts Treg recirculation back to the thymus, refining its functional repertoire.

    Evidence Glycosylation-site mutagenesis with migration/endocytosis assays; Rag2pGFPCcr7-/- thymic Treg analysis

    PMID:26819318 PMID:26832402

    Open questions at the time
    • Enzymes deglycosylating CCR7 in vivo not fully characterized
    • Mechanism of CCR7-mediated thymic re-entry restriction unclear
  16. 2017 Medium

    Defined biophysical determinants of CCR7 function: homodimerization enhances migration/signaling, and N-terminal sulfotyrosines (Y8, Y17) boost CCL21 binding.

    Evidence Chemically induced dimerization and disruptor peptide with BRET/FRET; NMR of sulfopeptide-CCL21 binding

    PMID:28819198 PMID:28841151

    Open questions at the time
    • NMR sulfotyrosine study lacks cell-based functional validation
    • Endogenous regulation of sulfation/dimerization not established
  17. 2018 High

    Linked cellular metabolism to receptor biophysics, showing glycolysis supports CCR7 oligomerization and DC migratory capacity.

    Evidence Glycolysis inhibition, oligomerization assays, in vivo DC migration, metabolic profiling

    PMID:29941886

    Open questions at the time
    • Molecular link between glycolytic flux and oligomerization not defined
    • Single lab
  18. 2019 High

    Resolved CCR7 signaling into spatially organized and modular outputs and uncovered metabolic feedback, including an endomembrane Src-Vav1-Rac1 complex, independent PI3K/MAPK/RhoA modules, HIF-1α glycolytic reprogramming with lnc-Dpf3 feedback, and CXCR4 heteromerization.

    Evidence Co-IP, Src mutagenesis, Rac1 photoactivation, pharmacological module dissection, DC-specific lnc-Dpf3 KO with RIP, BRET heteromerization assays

    PMID:30824325 PMID:31644919 PMID:31921208 PMID:32351499

    Open questions at the time
    • Integration of the modular pathways into a unified migratory program incomplete
    • In vivo relevance of CXCR4 heteromer effects limited to B cell models
  19. 2022 High

    Established CCR7's role in neutrophil clearance to draining lymph nodes and revealed ACKR4-mediated CCL19/CCL21 scavenging as an external regulator enabling lymphatic transport.

    Evidence Neutrophil-specific CCR7 deletion with photoconvertible tracking and S. aureus model; ACKR4-deficient mice with intravital lymphatic imaging

    PMID:35108538 PMID:35119939

    Open questions at the time
    • Crosstalk between cell-intrinsic CCR7 signaling and ACKR4 scavenging not fully integrated
    • Mechanism of cDC phagocytosis of CCR7+ neutrophils not detailed
  20. 2023 High

    Demonstrated CCR7 acts as a chemokine sink shaping its own gradients for collective migration, and as a PI3Kγ-dependent survival signal exploited by lymphoma.

    Evidence Microfluidic gradient chambers with live imaging and modeling; CCR7 genetic deletion in ALCL model with PI3Kγ/δ inhibition and PDX

    PMID:37379367 PMID:37656776

    Open questions at the time
    • In vivo confirmation of self-generated gradients in tissue not established
    • Therapeutic targeting of CCR7-PI3Kγ axis only tested in limited lymphoma models

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct CCR7 signaling modules, trafficking states, post-translational modifications, and dimerization are integrated in space and time to produce a single coherent migratory response remains unresolved.
  • No unified structural model linking C-terminal motifs, ubiquitylation, glycosylation, and dimerization
  • The ubiquitin ligase and deglycosylating enzymes acting on CCR7 in vivo are unidentified
  • Quantitative rules governing ligand discrimination between CCL19 and CCL21 signaling outcomes are incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 1 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1643685 Disease 3
Partners
ACKR4ARRB (Β-ARRESTIN)CCL19CCL21CXCR4RAC1SRCVAV1
Complex memberships
CCR7 homodimerCCR7-CXCR4 heteromerendomembrane CCR7-Src-Vav1-Rac1 signaling complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 ELC (CCL19) was identified as a specific, high-affinity functional ligand for CCR7 (EBI1): ELC-SEAP bound specifically to CCR7-transfected cells, only ELC competed for binding among tested CC chemokines, and ELC induced calcium mobilization and chemotaxis in CCR7-expressing cells. Receptor-binding assay with alkaline phosphatase fusion protein, calcium mobilization assay, chemotaxis assay in stably transfected cells The Journal of biological chemistry High 9153236
1998 CCR7 is coupled to a Gαi protein: CK beta-11/MIP-3β/ELC-induced chemotaxis and actin polymerization in lymphocytes were completely blocked by pertussis toxin, and ELC induced calcium mobilization that could be cross-desensitized by SDF-1. Pertussis toxin inhibition of chemotaxis, calcium mobilization assay, actin polymerization assay Journal of immunology High 9498785
1998 CCR7 (EBI1) expression is dramatically up-regulated upon dendritic cell maturation (in mouse bone marrow-derived DCs, Langerhans cells, and human monocyte-derived DCs), and the induced CCR7 is functional, mediating calcium mobilization and directional migration toward ELC/MIP-3β in mature but not immature DCs. Flow cytometry, calcium mobilization assay, chemotaxis assay in mature vs. immature DC cultures Journal of immunology High 9743376
2003 Rho kinase (ROCK) is required for CCR7-mediated T lymphocyte polarization and chemotaxis: inhibition with Y-27632 strongly blocked SLC/CCL21- and ELC/CCL19-induced polarized morphology and chemotaxis, whereas ERK2 inhibition had no effect on these processes. Rho kinase inhibitor (Y-27632) treatment, ERK inhibitor treatment, polarization and chemotaxis assays in T lymphocytes FEBS letters Medium 12729902
2004 CCR7 governs entry of both dermal and epidermal dendritic cells into lymphatic vessels within the dermis under inflammatory and steady-state conditions, and is required for the presence of a semimature CD11c+MHCIIhigh DC population in skin-draining lymph nodes, as demonstrated by near-complete absence of these cells in CCR7-deficient mice. CCR7-deficient mouse analysis, immunohistology, flow cytometry of skin-draining lymph nodes Immunity High 15308107
2004 CCR7 is required for intrathymic migration of early T cell progenitors toward the outer cortex: CCR7-deficient mice show disturbed thymic architecture, accumulation of CD25intCD44+ double-negative cells at the cortico-medullary junction, impaired T cell development, and decreased thymocyte numbers; mixed bone marrow chimeras confirmed the cell-intrinsic requirement. CCR7-deficient mouse analysis, immunohistology, flow cytometry, mixed bone marrow chimeras The Journal of experimental medicine High 15302903
2005 CCR7 is a critical signal determining T cell exit from peripheral tissue into afferent lymphatics: CCR7+ but not CCR7− effector T cells migrated from asthmatic lung into afferent lymph and draining lymph nodes, establishing a molecular basis for T cell retrograde tissue egress. Adoptive transfer of CCR7+ vs. CCR7− T cells into mouse asthmatic lung; flow cytometry of afferent lymph and draining lymph nodes Nature immunology High 16116469
2008 Distinct C-terminal motifs of CCR7 regulate different signaling outputs: a Ser/Thr motif at the tip of the intracellular tail controls chemokine-mediated Erk1/2 activation; an adjacent regulatory motif modulates this; a region encompassing the full C-terminus is required for G-protein coupling, Ca2+ mobilization, Erk1/2 phosphorylation, and chemotaxis; receptor trafficking/internalization occurs independently of G-protein coupling. C-terminal deletion mutants and G-protein-coupling-impaired CCR7 mutants; Ca2+ mobilization, Erk1/2 phosphorylation, chemotaxis, and internalization assays Journal of cell science High 18664492
2008 In secondary lymphoid organs, T cell surface CCR7 is largely occupied by CCL19, leading to continuous signaling and reduced chemotactic responsiveness; both CCL19 and CCL21 trigger CCR7 internalization in vivo; CCR7 occupancy/down-regulation causes strongly impaired chemotactic responses that are reversible by resensitization. In vivo CCR7 occupancy analysis in Ccl19−/− and plt/plt mice; flow cytometry; in vitro chemotaxis after receptor resensitization Journal of immunology Medium 19017956
2010 The actin-bundling protein L-plastin (LPL) is required for CCR7-mediated T cell polarization and chemotaxis but is dispensable for CCR7 proximal signaling (F-actin polymerization) and CCR7-mediated costimulation: LPL−/− T cells fail to polarize CCR7 to the leading edge upon chemokine stimulation; mature LPL−/− thymocytes show diminished thymic egress in vivo. LPL−/− mouse, two-photon microscopy of lymphocyte motility, CCR7 localization imaging, chemotaxis assays, thymic egress assays Journal of immunology High 20194718
2012 CCR7 is constitutively ubiquitylated in a ligand-independent manner; upon CCL19 binding, internalized CCR7 recycles back to the plasma membrane via the trans-Golgi network. A ubiquitylation-deficient CCR7 mutant internalizes normally but recycles inefficiently and is retained in the trans-Golgi network, profoundly impairing immune cell migration. Ubiquitylation-deficient CCR7 mutant; receptor trafficking assays; trans-Golgi network colocalization; immune cell migration assays Journal of cell science High 22797918
2012 CCR7/CCL19 signaling activates ERK5, which drives sequential upregulation of the transcription factor KLF-2 and then EDG-1 (S1PR1), thereby controlling T cell egress from lymph nodes; ERK5-deleted T cells (ERK5flox/flox/Lck-Cre) failed to increase migration toward EDG-1 ligands after CCL19 stimulation. CCL19 stimulation of HuT78 cells and primary murine T cells; ERK5flox/flox/Lck-Cre conditional knockout; Western blot; migration assay The Journal of biological chemistry Medium 22334704
2013 CCR7 signaling localizes Treg cells expressing CCR7 to T cell zones of secondary lymphoid tissues where paracrine IL-2 is available, selectively maintaining a CD44loCD62Lhi Treg subset; CCR7lo Tregs in nonlymphoid tissues are IL-2-insensitive and instead depend on ICOS signaling. CCR7 reporter/KO mice; in vivo IL-2 blockade; ICOS blockade; flow cytometry of tissue-specific Treg subsets The Journal of experimental medicine High 24378538
2016 CCR7 is N-glycosylated at two specific residues (in the N-terminus and the third extracellular loop); the glycosylation pattern modulates receptor sensitivity and endocytosis. Dendritic cells enhance T cell migration toward CCR7 ligands by secreting deglycosylating enzymes that remove sialic acid from CCR7, boosting CCR7 signaling and decreasing receptor endocytosis. DCs also proteolytically convert immobilized CCL21 to a soluble form with distinct signaling properties. Site-directed mutagenesis of glycosylation sites; metabolic glycan labeling; flow cytometry; migration assays; DC co-culture experiments Journal of leukocyte biology High 26819318
2017 CCR7 homodimerization directly contributes to CCR7-dependent cell migration and signaling: induction of stable CCR7 homodimers enhanced migration and CCL19 binding, whereas a CCR7-derived synthetic peptide that disrupts homodimers attenuated migration, receptor internalization, actin rearrangement, and Akt/Erk signaling. Induction of CXCR4/CCR7 heterodimers did not enhance migration. Chemically induced dimerization; CCR7-derived peptide to disrupt dimers; BRET/FRET dimerization assays; chemotaxis, signaling, and internalization assays Scientific reports Medium 28819198
2017 Sulfotyrosine at positions Y8 and Y17 of the CCR7 N-terminus enhances binding to CCL21: NMR showed sulfotyrosine-containing CCR7 peptides have greater affinity than tyrosine or phosphotyrosine peptides; sY8-containing peptides bind near the CCL21 α-helix, sY17-containing peptides bind near the N-loop and β3-strand. Protein NMR spectroscopy with synthetic sulfopeptides, phosphopeptides, and unmodified peptides; binding affinity measurements International journal of molecular sciences Medium 28841151
2018 Inhibition of glycolysis impaired CCR7 oligomerization and dendritic cell migration to draining lymph nodes; early glycolytic activation (via AKT, TBK, mTOR) is a common program accompanying DC activation and supports DC migratory ability and elongated cell shape independently of mitochondrial bioenergetics. Glycolysis inhibition assays; CCR7 oligomerization assays; DC migration to draining lymph nodes in vivo; metabolic profiling Nature communications High 29941886
2019 CCR7 stimulation activates HIF-1α-dependent glycolytic reprogramming (including Ldha transcription) in dendritic cells to support migration. A CCR7-inducible lncRNA (lnc-Dpf3) feeds back to suppress this by directly binding HIF-1α and blocking its transcriptional activity, thereby limiting DC glycolytic metabolism and migratory capacity. CCR7 stimulation upregulates lnc-Dpf3 via m6A demethylation to prevent RNA degradation. DC-specific lnc-Dpf3 knockout mice; RIP assay (lnc-Dpf3/HIF-1α interaction); DC migration assays; metabolic assays; m6A modification analysis Immunity High 30824325
2019 CCR7 uses distinct signaling modules with biased functionality in dendritic cells: the PI3K/Akt pathway controls DC survival, the MAPK pathway controls chemotaxis, and the RhoA pathway controls actin dynamics (migratory speed, cytoarchitecture, and endocytosis); these three pathways function as largely independent modules. Pharmacological inhibitors of PI3K/Akt, MAPK, and RhoA pathways; functional assays for DC survival, chemotaxis, migration speed, and endocytosis Frontiers in immunology Medium 32351499
2019 CCR7 forms heteromers with CXCR4 during B cell development; upregulation of CCR7 selectively impairs CXCR4's ability to activate certain G-protein complexes, reducing CXCR4 responsiveness to CXCL12 and decreasing B cell retention in bone marrow. CCR7−/− mature B cells display higher CXCL12 responsiveness and increased bone marrow retention. CCR7−/− mouse; CXCL12-induced calcium flux and chemotaxis assays; BRET-based heteromerization assays; bone marrow retention assays Frontiers in immunology Medium 31921208
2019 CCR7 signaling activates the CCR7 → Sp1 → heparanase axis in lung cancer cells: CCL19 stimulation of CCR7 upregulated Sp1 and heparanase mRNA/protein; CCR7 blockade suppressed this; Sp1 inhibition downregulated heparanase; ChIP showed Sp1 binds the heparanase promoter; this pathway promotes cell invasion. CCL19 stimulation, CCR7 blockade, Sp1 inhibition, chromatin immunoprecipitation (ChIP), invasion assays in A549 cells Tumour biology Medium 23649655
2019 CCR7 signaling initiates an endomembrane signaling complex for spatial Rac1 activation during cell migration: CCR7 at the plasma membrane traffics with β-arrestin and Src kinase to endomembranes; Src phosphorylates CCR7 at endomembranes; phospho-CCR7 recruits the RhoGEF Vav1; Vav1 activates Rac1 locally. Photoactivation of Rac1 at endomembranes produced lamellipodia at the leading edge. Co-immunoprecipitation; Src kinase mutagenesis; vesicular trafficking inhibition; proximity ligation assay; Rac1 photoactivation; cell migration assays in dendritic cells Cell reports High 31644919
2022 ACKR4 (atypical chemokine receptor 4) acts as a scavenger of CCL19 and CCL21 in lymphatic collecting vessel endothelial cells, induced by lymph flow; this enables de-adhesion of T cells in collecting vessels for passive transport to draining lymph nodes. In ACKR4-deficient mice, T cells accumulate in dermal collecting segments and LN migration is reduced despite normal capillary entry. ACKR4-deficient mice; TPA-induced skin inflammation; flow cytometry; intravital microscopy of lymphatic vessels; endothelial ACKR4 induction by flow Cell reports Medium 35108538
2023 CCR7 acts both as a sensory receptor steering migration and as an effective sink for CCL19: upon ligand binding, DCs internalize CCR7 and ligand via canonical GPCR desensitization, which depletes local CCL19 and self-generates/sharpens chemotactic gradients. This enables collective DC migration, long-range guidance, and gradient sharing with comigrating cells. Microfluidic gradient chambers; live cell imaging of DC migration; mathematical modeling; CCR7 internalization assays; collective migration analysis Science immunology High 37656776
2007 CCR7 mediates corneal antigen-presenting cell trafficking to draining lymph nodes via interaction with CCL21: CCR7+ CD11b+CD11c+ cells localized near LYVE-1+ lymphatic vessels in inflamed corneas; CCR7+ OVA-loaded APCs appeared in draining LNs 48h after transplantation; local anti-CCL21 antibody neutralization significantly suppressed OVA+CD11c+ cell flow to draining LNs. Corneal transplant with fluorescent OVA tracking; anti-CCL21 neutralizing antibody injection; flow cytometry; immunofluorescence Molecular vision Medium 17515886
2006 Endothelins induce CCR7 expression in breast tumor cells via endothelin receptor A and HIF-1α: endothelin stimulation stabilized HIF-1α, which drove CCR7 transcription; dominant-negative HIF-1α abolished CCR7 induction; CCR7-dependent endothelin-mediated invasion was blocked by anti-CCR7 antibody. Dominant-negative HIF-1α transfection; iron chelator treatment; CCR7-neutralizing antibody; invasion assay; flow cytometry Cancer research Medium 17178876
2007 CCR7 signaling inhibits T cell proliferation and induces cell cycle arrest: sustained high concentrations of CCL19 or CCL21 (soluble or immobilized) specifically blocked proliferation and IL-2 secretion in CCR7+ T cells (human and murine CD4+ and CD8+); this was associated with delayed degradation of p27Kip1 and down-regulation of CDK1; CCR7−/− T cells showed normal proliferation unaffected by CCL19. CCR7−/− mouse T cells; proliferation assays; ELISA for IL-2; Western blot for p27Kip1 and CDK1; comparison of soluble vs. immobilized ligands Journal of immunology Medium 17982037
2009 Jak3 is required for CCR7-mediated dendritic cell migration: Jak3−/− DCs show impaired chemotactic responses to CCL19 and CCL21 both in vitro and in vivo, and reduced DC-mediated T lymphocyte activation, while DC generation from bone marrow progenitors is unaffected. Jak3−/− mice; in vitro and in vivo DC chemotaxis assays; mixed lymphocyte reactions; contact hypersensitivity assay PloS one Medium 19759904
2016 CCR7 limits Treg recirculation back to the thymus: CCR7 defines bona fide Rag2GFP+ Treg precursors in the thymus, but CCR7 is not required for Treg production or emigration; lack of CCR7 renders the thymus more receptive to Treg thymus homing, revealing CCR7 functions to restrict re-entry of peripheral Tregs. Rag2pGFPCcr7−/− mice; intrathymic labeling; flow cytometry; thymic Treg precursor developmental analysis Cell reports Medium 26832402
2014 Epigenetic silencing via H3K27me3 at the Ccr7 promoter restricts CCR7 expression to conventional DCs (cDCs) but not monocyte-derived DCs (moDCs): moDCs were enriched for H3K27me3 at the Ccr7 locus compared to migratory cDCs, explaining their failure to migrate efficiently to lymph nodes. This silencing occurs gradually during monocyte-to-moDC differentiation rather than at early lineage commitment. ChIP for H3K27me3 at Ccr7 locus in lung DC subsets; bone marrow-derived DC cultures; in vivo DC migration assays Journal of immunology Medium 25297875
2015 FOXO1 transcriptionally regulates CCR7 expression in dendritic cells: FOXO1 binds the CCR7 promoter directly, stimulates CCR7 transcriptional activity, and regulates CCR7 expression; rescue of FOXO1-deleted DCs with both CCR7 and ICAM-1 expression reverses impaired DC homing to lymph nodes in vivo. FOXO1 promoter-binding ChIP; transcriptional activity assay; conditional FOXO1 knockout (CD11c.Cre); rescue transfection; in vivo DC homing assay Journal of immunology Medium 25786691
2023 CCR7 activates PI3Kγ signaling in ALK+ ALCL lymphoma cells as a survival pathway; endothelial-derived CCL19/CCL21 protected ALCL cells from crizotinib-induced apoptosis in a 3D microfluidic chip; genetic deletion of CCR7 blocked CNS dissemination and perivascular growth of ALCL in crizotinib-treated mice; dual PI3Kγ/δ inhibition with duvelisib potentiated crizotinib activity. 3D microfluidic chip; CCR7 genetic deletion in mouse ALCL model; PI3Kγ/δ inhibitor (duvelisib) combination; patient-derived xenografts Science translational medicine Medium 37379367
2022 CCR7 mediates neutrophil migration from inflamed or infected skin to draining lymph nodes via lymphatic vessels; in the dLNs, CCR7+ neutrophils are phagocytosed by cDC1 and cDC2; CCR7-specific deficiency in neutrophils increased antistaphylococcal immunity and aggravated skin inflammation, establishing a regulatory role for CCR7-dependent neutrophil LN homing in cutaneous immunity. Conditional CCR7-deficient neutrophils; photoconvertible mouse tracking; Staphylococcus aureus skin infection model; TLR-induced inflammation; flow cytometry Science immunology High 35119939
1995 BLR2/EBI1/CCR7 mRNA expression is specifically transactivated by Epstein-Barr virus nuclear antigen 2 (EBNA2): estrogen-inducible EBNA2 in EBV-negative BL41 cells drove BLR2 transcription, identifying EBNA2 as a transcriptional activator of CCR7 in B cells. Northern blot; estrogen-inducible EBNA2 expression system in EBV-negative BL41 cells; RT-PCR Biochemical and biophysical research communications Medium 7488016

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 CCR7 and its ligands: balancing immunity and tolerance. Nature reviews. Immunology 1151 18379575
2004 CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 805 15308107
2005 Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics. Nature immunology 420 16116469
1997 Molecular cloning of a novel human CC chemokine EBI1-ligand chemokine that is a specific functional ligand for EBI1, CCR7. The Journal of biological chemistry 325 9153236
2013 CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets. The Journal of experimental medicine 321 24378538
2019 CCR7 Chemokine Receptor-Inducible lnc-Dpf3 Restrains Dendritic Cell Migration by Inhibiting HIF-1α-Mediated Glycolysis. Immunity 302 30824325
1998 EBI1/CCR7 is a new member of dendritic cell chemokine receptor that is up-regulated upon maturation. Journal of immunology (Baltimore, Md. : 1950) 286 9743376
2002 Expression of chemokine receptor CCR7 is associated with lymph node metastasis of gastric carcinoma. Cancer research 266 12019175
2001 CCR7 expression and memory T cell diversity in humans. Journal of immunology (Baltimore, Md. : 1950) 255 11145663
2005 IL-18-induced CD83+CCR7+ NK helper cells. The Journal of experimental medicine 236 16203865
2004 Expression of CCR7 in multiple sclerosis: implications for CNS immunity. Annals of neurology 223 15122702
2018 Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration. Nature communications 177 29941886
2019 CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant Functions in Viral Infection and Prevention. Frontiers in cell and developmental biology 162 31632965
2016 Common and biased signaling pathways of the chemokine receptor CCR7 elicited by its ligands CCL19 and CCL21 in leukocytes. Journal of leukocyte biology 159 26729814
2004 Thymic T cell development and progenitor localization depend on CCR7. The Journal of experimental medicine 157 15302903
2004 CCL21 chemokine regulates chemokine receptor CCR7 bearing malignant melanoma cells. Clinical cancer research : an official journal of the American Association for Cancer Research 151 15073111
2021 Dendritic Cells and CCR7 Expression: An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer. International journal of molecular sciences 111 34361107
2000 Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells. Blood 107 10607681
1998 CK beta-11/macrophage inflammatory protein-3 beta/EBI1-ligand chemokine is an efficacious chemoattractant for T and B cells. Journal of immunology (Baltimore, Md. : 1950) 102 9498785
2020 CCR7 as a therapeutic target in Cancer. Biochimica et biophysica acta. Reviews on cancer 94 33385485
2000 Cytokines and cell surface molecules independently induce CXCR4 expression on CD4+ CCR7+ human memory T cells. Journal of immunology (Baltimore, Md. : 1950) 92 10878344
2020 CCL21/CCR7 interaction promotes EMT and enhances the stemness of OSCC via a JAK2/STAT3 signaling pathway. Journal of cellular physiology 88 32017846
1998 EBI1-ligand chemokine (ELC) attracts a broad spectrum of lymphocytes: activated T cells strongly up-regulate CCR7 and efficiently migrate toward ELC. International immunology 86 9701028
2020 The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression. Cancers 80 32340161
1995 Expression of the chemokine receptor BLR2/EBI1 is specifically transactivated by Epstein-Barr virus nuclear antigen 2. Biochemical and biophysical research communications 77 7488016
1994 Cloning of human and mouse EBI1, a lymphoid-specific G-protein-coupled receptor encoded on human chromosome 17q12-q21.2. Genomics 76 7851893
2022 New Insights of CCR7 Signaling in Dendritic Cell Migration and Inflammatory Diseases. Frontiers in pharmacology 75 35281921
2004 Impact of CCR7 on priming and distribution of antiviral effector and memory CTL. Journal of immunology (Baltimore, Md. : 1950) 71 15557160
2007 The chemokine receptor CCR7 mediates corneal antigen-presenting cell trafficking. Molecular vision 70 17515886
2016 Distinct CCR7 glycosylation pattern shapes receptor signaling and endocytosis to modulate chemotactic responses. Journal of leukocyte biology 67 26819318
2014 CCR7: roles in cancer cell dissemination, migration and metastasis formation. The international journal of biochemistry & cell biology 64 25019368
2016 CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3(+) T Cells. Cell reports 58 26832402
2013 The chemokine receptor CCR7 expressed by dendritic cells: a key player in corneal and ocular surface inflammation. The ocular surface 58 24725321
2006 CCR7 mediates inflammation-associated tumor progression. Immunologic research 57 17337767
2024 Tumour-retained activated CCR7+ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity. Nature communications 55 38267413
2000 Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and are produced by distinct subsets of medullary epithelial cells: possible implications for negative selection. Journal of immunology (Baltimore, Md. : 1950) 55 10861057
1998 Macrophage-inflammatory protein-3 beta/EBI1-ligand chemokine/CK beta-11, a CC chemokine, is a chemoattractant with a specificity for macrophage progenitors among myeloid progenitor cells. Journal of immunology (Baltimore, Md. : 1950) 55 9725259
2006 Expression and function of the chemokine receptor CCR7 in thyroid carcinomas. The Journal of endocrinology 54 17065406
2006 Endothelins induce CCR7 expression by breast tumor cells via endothelin receptor A and hypoxia-inducible factor-1. Cancer research 53 17178876
2003 Rho kinase is required for CCR7-mediated polarization and chemotaxis of T lymphocytes. FEBS letters 53 12729902
2018 The chemokine receptor CCR7 is a promising target for rheumatoid arthritis therapy. Cellular & molecular immunology 52 29973648
2016 CXCR4 and CCR7: Two eligible targets in targeted cancer therapy. Cell biology international 52 27248053
2017 Regulation of CCR7-dependent cell migration through CCR7 homodimer formation. Scientific reports 51 28819198
2012 Multifaceted activities of CCR7 regulate T-cell homeostasis in health and disease. European journal of immunology 51 22700449
2003 Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking. Microcirculation (New York, N.Y. : 1994) 51 12851649
2015 FOXO1 regulates dendritic cell activity through ICAM-1 and CCR7. Journal of immunology (Baltimore, Md. : 1950) 50 25786691
2008 Chemokine receptor CCR7 expression correlates with lymph node metastasis in pancreatic cancer. Oncology 49 18544997
2020 The Chemokine Receptor CCR7 Uses Distinct Signaling Modules With Biased Functionality to Regulate Dendritic Cells. Frontiers in immunology 47 32351499
2016 Human NK Cell Subsets Redistribution in Pathological Conditions: A Role for CCR7 Receptor. Frontiers in immunology 44 27774094
2008 Functional expression of the chemokine receptor CCR7 on fibroblast-like synoviocytes. Rheumatology (Oxford, England) 44 18838387
2023 CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science immunology 43 37656776
2014 CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye disease. Investigative ophthalmology & visual science 43 25139737
2010 The actin-bundling protein L-plastin dissociates CCR7 proximal signaling from CCR7-induced motility. Journal of immunology (Baltimore, Md. : 1950) 43 20194718
2012 Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration. Journal of cell science 42 22797918
2014 Contribution of homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 to coronary artery disease. Arteriosclerosis, thrombosis, and vascular biology 40 24990231
2013 CCL19/CCR7 upregulates heparanase via specificity protein-1 (Sp1) to promote invasion of cell in lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 23649655
2008 Distinct motifs in the chemokine receptor CCR7 regulate signal transduction, receptor trafficking and chemotaxis. Journal of cell science 40 18664492
2008 Dynamic modulation of CCR7 expression and function on naive T lymphocytes in vivo. Journal of immunology (Baltimore, Md. : 1950) 40 19017956
2007 CCR7 signaling inhibits T cell proliferation. Journal of immunology (Baltimore, Md. : 1950) 39 17982037
2019 Coexpression of CCR7 and CXCR4 During B Cell Development Controls CXCR4 Responsiveness and Bone Marrow Homing. Frontiers in immunology 38 31921208
2010 Chicken CCR6 and CCR7 are markers for immature and mature dendritic cells respectively. Developmental and comparative immunology 36 21195108
2020 The pathogenic importance of CCL21 and CCR7 in rheumatoid arthritis. Cytokine & growth factor reviews 35 32499193
2016 CCR7 Maintains Nonresolving Lymph Node and Adipose Inflammation in Obesity. Diabetes 35 27207557
2015 The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells. Oncogene 35 25772241
2023 CCL21/CCR7 axis as a therapeutic target for autoimmune diseases. International immunopharmacology 34 37331295
2017 Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization. Oncotarget 33 28416768
2005 Oral and oropharyngeal squamous cell carcinomas expressing CCR7 have poor prognoses. Auris, nasus, larynx 33 16223574
2015 Differential ligand-signaling network of CCL19/CCL21-CCR7 system. Database : the journal of biological databases and curation 32 26504105
2014 Epigenetic control of Ccr7 expression in distinct lineages of lung dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 32 25297875
2006 Focal interstitial CC chemokine receptor 7 (CCR7) expression in idiopathic interstitial pneumonia. Journal of clinical pathology 32 16394278
2006 Chemokine receptor CCR7 enhances intrahepatic and lymphatic dissemination of human hepatocellular cancer. Oncology reports 32 16786131
2022 CCR7-guided neutrophil redirection to skin-draining lymph nodes regulates cutaneous inflammation and infection. Science immunology 29 35119939
2020 CCL19 suppresses gastric cancer cell proliferation, migration, and invasion through the CCL19/CCR7/AIM2 pathway. Human cell 29 32564199
2019 Chemokine Receptor CCR7 Triggers an Endomembrane Signaling Complex for Spatial Rac Activation. Cell reports 29 31644919
2010 CCR7 is expressed in astrocytes and upregulated after an inflammatory injury. Journal of neuroimmunology 29 20638137
2009 Jak3 is involved in dendritic cell maturation and CCR7-dependent migration. PloS one 29 19759904
2022 Mechanosensitive ACKR4 scavenges CCR7 chemokines to facilitate T cell de-adhesion and passive transport by flow in inflamed afferent lymphatics. Cell reports 28 35108538
2009 CCR7 regulates lymphocyte egress and recirculation through body cavities. Journal of leukocyte biology 28 20028772
2020 CCR7 as a novel therapeutic target in t-cell PROLYMPHOCYTIC leukemia. Biomarker research 27 33110606
2019 Elevated CCL19/CCR7 Expression During the Disease Process of Primary Sjögren's Syndrome. Frontiers in immunology 27 31068931
2017 Biased signaling of G protein-coupled receptors - From a chemokine receptor CCR7 perspective. General and comparative endocrinology 27 28694053
2014 Dry eye-induced CCR7+CD11b+ cell lymph node homing is induced by COX-2 activities. Investigative ophthalmology & visual science 27 25257053
2005 Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease. Journal of clinical pathology 27 16189151
2018 Fluorescently Tagged CCL19 and CCL21 to Monitor CCR7 and ACKR4 Functions. International journal of molecular sciences 26 30518137
2012 CCR7/CCL19 controls expression of EDG-1 in T cells. The Journal of biological chemistry 26 22334704
2022 CXCL12 promotes CCR7 ligand-mediated breast cancer cell invasion and migration toward lymphatic vessels. Cancer science 24 35133060
2017 Interplay between CCR7 and Notch1 axes promotes stemness in MMTV-PyMT mammary cancer cells. Molecular cancer 24 28137279
2014 Correlation between CCR7 expression and lymph node metastatic potential of human tongue carcinoma. Oral diseases 24 24528991
2011 Deficient CCR7 signaling promotes TH2 polarization and B-cell activation in vivo. European journal of immunology 24 21969271
2014 CCR7-mediated migration in the thymus controls γδ T-cell development. European journal of immunology 23 24500801
2023 CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma. Cellular and molecular life sciences : CMLS 22 37314567
2020 Down-regulation of CCR7 via AKT pathway and GATA2 inactivation suppressed trophoblast migration and invasion in recurrent spontaneous abortion†. Biology of reproduction 22 31504210
2015 Curcumin treatment suppresses CCR7 expression and the differentiation and migration of human circulating fibrocytes. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 22 25613752
2012 oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21. Mediators of inflammation 22 22619482
2023 Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma. Science translational medicine 20 37379367
2019 CCL21-expression and accumulation of CCR7+ NK cells in livers of patients with primary sclerosing cholangitis. European journal of immunology 20 30785638
2021 CCR7 in Blood Cancers - Review of Its Pathophysiological Roles and the Potential as a Therapeutic Target. Frontiers in oncology 19 34778050
2017 CCR7 Sulfotyrosine Enhances CCL21 Binding. International journal of molecular sciences 19 28841151
2008 SOCS1 regulates CCR7 expression and migration of CD4+ T cells into peripheral tissues. Journal of immunology (Baltimore, Md. : 1950) 19 18606672
2007 Expression of chemokine receptors CCR7 and CCR8 in the CNS during ChREAE. Scandinavian journal of immunology 19 17850582

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