Affinage

CCR7

C-C chemokine receptor type 7 · UniProt P32248

Length
378 aa
Mass
42.9 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCR7 is a Gαi-coupled chemokine receptor that directs the migration and positioning of T cells, dendritic cells, and other leukocytes to and within secondary lymphoid organs by sensing gradients of its two ligands, CCL19 and CCL21. Signaling proceeds through largely independent downstream modules: PI3K/Akt promotes cell survival, MAPK governs chemotaxis, and RhoA/Rho kinase controls actin dynamics and cell polarization; additionally, CCR7 activates JAK2, ERK5–KLF-2 (upregulating S1P1 for lymph node egress), and HIF-1α (driving glycolytic reprogramming), while internalized CCR7–β-arrestin–Src complexes signal from endomembranes to recruit Vav1 and Rac1, sustaining lamellipodia formation during directed migration (PMID:9498785, PMID:12729902, PMID:12393730, PMID:22334704, PMID:30824325, PMID:31644919, PMID:32351499). CCL19 induces rapid CCR7 internalization, desensitization, and self-generated chemokine gradient depletion that enables collective long-range guidance, whereas CCL21 does not trigger internalization, permitting persistent surface signaling; receptor function is further tuned by N-glycosylation/sialylation, homodimerization, glycolysis-dependent oligomerization, transcriptional regulation by FOXO1, EBNA2, and Notch1, and epigenetic silencing by H3K27me3 (PMID:11745346, PMID:37656776, PMID:26819318, PMID:28819198, PMID:29941886, PMID:25786691, PMID:7488016, PMID:19536265, PMID:25297875). Beyond homeostatic lymphocyte homing, CCR7 is co-opted in disease: Notch1-driven CCR7 expression mediates T-ALL infiltration of the CNS, CCR7-dependent PI3Kγ signaling confers resistance to ALK inhibitors in ALCL, and CCR7 on breast cancer cells promotes lymphangiogenesis via AKT-driven VEGF-C secretion (PMID:19536265, PMID:37379367, PMID:25744065).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1995 Medium

    Before any ligand was known, EBNA2 was shown to transcriptionally activate the orphan receptor EBI1 (later CCR7) in B cells, establishing the gene as an EBV-responsive locus even before its chemokine receptor identity was understood.

    Evidence Northern blot with estrogen-inducible EBNA2 system in EBV-negative BL41 B cells

    PMID:7488016

    Open questions at the time
    • single inducible system without chromatin-level analysis
    • no demonstration of direct EBNA2 binding to the CCR7 promoter
    • functional consequence of EBNA2-induced CCR7 on B cell biology not tested
  2. 1997 High

    The identification of CCL19 as a specific high-affinity ligand for CCR7 deorphanized the receptor and established it as a functional chemokine receptor capable of triggering calcium flux and chemotaxis.

    Evidence Alkaline phosphatase-fused ligand binding, calcium mobilization, and chemotaxis assays across multiple transfected receptor lines

    PMID:9153236

    Open questions at the time
    • CCL21 not yet identified as a second ligand
    • G protein coupling not characterized
  3. 1998 High

    Pertussis toxin sensitivity demonstrated that CCR7 signals through Gαi, and CCL19 was shown to induce actin polymerization in primary lymphocytes, linking the receptor to cytoskeletal remodeling.

    Evidence Pertussis toxin blockade of chemotaxis, actin polymerization and calcium assays in primary T and B cells

    PMID:9498785

    Open questions at the time
    • downstream effectors between Gαi and actin not identified
    • relative contribution of Gαi vs. Gβγ not resolved
  4. 2001 High

    The discovery that CCL19 but not CCL21 triggers CCR7 internalization and desensitization revealed a fundamental asymmetry between the two ligands, raising the question of how the same receptor produces distinct cellular outcomes depending on which ligand it engages.

    Evidence Flow cytometry-based internalization and functional desensitization assays in T lymphocytes

    PMID:11745346

    Open questions at the time
    • molecular basis for differential internalization (β-arrestin recruitment difference) not yet determined
    • in vivo significance of differential desensitization unknown
  5. 2002 High

    JAK2 phosphorylation downstream of CCR7 and inhibition of chemotaxis/integrin activation by JAK inhibitor AG490 revealed a JAK-dependent signaling arm linking CCR7 to lymphocyte adhesion in high endothelial venules in vivo.

    Evidence AG490 treatment, intravital microscopy of HEV adhesion, JAK2 phosphorylation western blot in primary lymphocytes

    PMID:12393730

    Open questions at the time
    • which JAK isoform is essential (JAK2 vs. JAK3) not fully resolved
    • direct physical JAK–CCR7 interaction not shown
  6. 2003 Medium

    Rho kinase was identified as required for CCR7-mediated T cell polarization and chemotaxis, while ERK was dispensable, beginning to dissect signal-specific pathway modules downstream of the receptor.

    Evidence Y-27632 (Rho kinase inhibitor) blockade of CCL19/CCL21-induced polarization and migration in T cells

    PMID:12729902

    Open questions at the time
    • pharmacological inhibitor specificity concerns
    • upstream RhoA activation by CCR7 not directly shown
    • RhoGEF identity unknown
  7. 2004 High

    CCR7 knockout mice revealed non-redundant in vivo roles: CCR7 is essential for DC entry into lymphatics and migration to draining lymph nodes, and separately for intrathymic migration of T cell progenitors, establishing CCR7 as a master regulator of immune cell positioning across tissues.

    Evidence CCR7-/- mice with flow cytometry, immunohistology, DC trafficking assays, and mixed bone marrow chimeras

    PMID:15302903 PMID:15308107

    Open questions at the time
    • relative contribution of CCL19 vs. CCL21 in each tissue not resolved
    • compensatory mechanisms in chronic KO not excluded
  8. 2007 High

    Beyond migration, CCR7 engagement was found to inhibit T cell proliferation and IL-2 secretion via delayed p27Kip1 degradation and CDK1 downregulation, revealing an unexpected anti-proliferative signaling function verified by CCR7-KO T cell hyperproliferation.

    Evidence Proliferation assays with soluble/immobilized CCL19/CCL21, CCR7-KO comparison, p27Kip1 and CDK1 western blots

    PMID:17982037

    Open questions at the time
    • pathway connecting Gαi to p27Kip1 stabilization not identified
    • physiological relevance of anti-proliferative signaling in SLOs not tested in vivo
  9. 2008 High

    In vivo occupancy studies showed that most surface CCR7 on T cells in secondary lymphoid organs is constitutively engaged by CCL19, explaining why transferred T cells have reduced chemokine sensitivity in lymph nodes and demonstrating continuous physiological CCR7 signaling.

    Evidence CCR7 occupancy analysis in Ccl19-/- and plt/plt mice with in vitro internalization validation

    PMID:19017956

    Open questions at the time
    • how continuous engagement affects T cell function beyond desensitization not fully explored
    • occupancy by CCL21 in vivo not quantified
  10. 2009 High

    Notch1 was identified as a transcriptional driver of CCR7 in T-ALL, and CCR7/CCL19 signaling was shown to be specifically required for leukemic T cell infiltration of the CNS, linking CCR7 to pathological tissue invasion.

    Evidence Gene expression profiling, genetic silencing of CCR7/CCL19 in mouse T-ALL models and human xenografts

    PMID:19536265

    Open questions at the time
    • whether pharmacological CCR7 blockade is therapeutically viable in CNS leukemia not tested
    • downstream signaling pathway mediating CNS entry not identified
  11. 2009 Medium

    CCR7 was found to control lymphocyte egress from body cavities—not just entry into lymph nodes—as CCR7-deficient mice accumulated T and B cells in peritoneal and pleural spaces, broadening the receptor's role to general lymphocyte recirculation.

    Evidence CCR7-KO mice, flow cytometry of peritoneal/pleural lavage, lymphocyte recirculation assays

    PMID:20028772

    Open questions at the time
    • which ligand (CCL19 or CCL21) mediates cavity egress unknown
    • mechanism of CCR7-dependent egress from serosal surfaces not dissected
  12. 2010 High

    L-plastin was identified as required for CCR7 polarization to the leading edge and T cell chemotaxis, but dispensable for CCR7-triggered F-actin polymerization, separating receptor signaling from spatial receptor redistribution during migration.

    Evidence LPL-/- mice, two-photon microscopy in lymph nodes, receptor localization imaging, thymic egress assays

    PMID:20194718

    Open questions at the time
    • direct LPL–CCR7 physical interaction not demonstrated
    • mechanism linking LPL to CCR7 membrane clustering unknown
  13. 2012 High

    CCR7/CCL19 was found to upregulate S1P receptor 1 (S1P1) expression via an ERK5→KLF-2 axis, revealing a cross-talk mechanism whereby CCR7 primes T cells for subsequent S1P1-dependent lymph node egress.

    Evidence ERK5-flox/Lck-Cre conditional KO, migration assays to S1P, western blot for pathway components

    PMID:22334704

    Open questions at the time
    • whether CCL21 activates the same ERK5–KLF-2 axis not tested
    • in vivo validation of CCR7-dependent S1P1 upregulation for LN egress not shown
  14. 2014 Medium

    Epigenetic profiling revealed that H3K27me3 silences the Ccr7 locus specifically in monocyte-derived DCs but not conventional DCs, explaining lineage-specific CCR7 expression and migratory capacity differences between DC subsets.

    Evidence ChIP-seq/ChIP-PCR for H3K27me3 in bone marrow-derived and lung DC subsets, monocyte differentiation time-course

    PMID:25297875

    Open questions at the time
    • identity of the histone methyltransferase responsible not determined
    • whether H3K27me3 removal can rescue moDC migration not tested
  15. 2015 High

    Multiple advances refined CCR7 regulation: FOXO1 was shown to directly bind and activate the CCR7 promoter in DCs (controlling in vivo LN homing), N-glycosylation/sialylation of two extracellular residues was found to dampen CCR7 signaling and endocytosis, and NMR mapping revealed overlapping CCR7/PSGL-1 binding sites on CCL19.

    Evidence ChIP and luciferase reporter for FOXO1, DC-specific FOXO1-KO with rescue; mutagenesis of glycosylation sites with functional assays; NMR structure of CCL19 with chemical shift perturbation

    PMID:25786691 PMID:26115234 PMID:26819318

    Open questions at the time
    • whether FOXO1 and epigenetic (H3K27me3) regulation are coordinated is unknown
    • structural basis of glycosylation effects on receptor conformation not resolved
    • functional consequence of PSGL-1/CCR7 competition for CCL19 in vivo not tested
  16. 2017 High

    CCR7 homodimerization was shown to enhance ligand binding, migration, and Akt/Erk signaling, as demonstrated by a synthetic peptide that disrupted dimers and attenuated all CCR7 functions, establishing oligomeric state as a regulatory mechanism.

    Evidence Bidirectional dimer induction/disruption with synthetic peptide, migration, binding, internalization, and signaling assays

    PMID:28819198

    Open questions at the time
    • structural basis of CCR7 dimer interface not determined
    • stoichiometry of active signaling complex unknown
    • in vivo relevance of dimerization not tested
  17. 2018 High

    Glycolytic metabolism was linked to CCR7 function: early glycolysis induction supports CCR7 oligomerization and DC motility, and PI3K/Akt, MAPK, and RhoA were confirmed as biased, largely independent signaling modules controlling survival, chemotaxis, and actin dynamics, respectively.

    Evidence Glycolysis inhibition (2-DG) with CCR7 oligomerization and DC migration assays; pathway-specific pharmacological dissection of DC functions

    PMID:29941886 PMID:35281921

    Open questions at the time
    • how glycolysis mechanistically promotes CCR7 oligomerization not resolved
    • whether metabolic requirement is specific to CCR7 or general for GPCRs not tested
  18. 2019 High

    Two major mechanistic advances defined endosomal and metabolic signaling: internalized CCR7/β-arrestin/Src complexes recruit Vav1–Rac1 at endomembranes to sustain lamellipodia formation; separately, CCR7 activates HIF-1α-driven glycolysis in DCs, with the lncRNA lnc-Dpf3 providing negative feedback by binding HIF-1α and suppressing Ldha transcription.

    Evidence Co-IP, proximity ligation, Rac1 photoactivation at endomembranes; DC-specific lnc-Dpf3 KO, RNA pull-down, m6A analysis, metabolic assays, in vivo DC migration

    PMID:30824325 PMID:31644919

    Open questions at the time
    • whether endomembrane signaling occurs with CCL21 (which poorly internalizes CCR7) not addressed
    • generality of lnc-Dpf3 feedback beyond DCs unknown
    • structural basis of Src phosphorylation site on CCR7 not mapped
  19. 2021 Medium

    Systematic BRET assays comparing CCL19 and CCL21 in a uniform background found both ligands activate G proteins and recruit β-arrestin, with CCL19 showing higher potency but no clear qualitative bias, challenging earlier models of strict ligand-biased agonism.

    Evidence BRET-based G protein and β-arrestin recruitment assays in defined cellular system

    PMID:33921794

    Open questions at the time
    • apparent conflict with in vivo differential internalization data not fully reconciled
    • assays in overexpression system may not recapitulate endogenous receptor density
    • lack of measurement of downstream effector bias (e.g., Akt vs. Erk)
  20. 2022 High

    CCR7's role extended to neutrophils: microbially stimulated neutrophils upregulate CCR7 and migrate to draining lymph nodes via lymphatics, where they are phagocytosed by DCs; separately, ACKR4 on lymphatic collector endothelium was identified as a scavenger of CCL19/CCL21 that shapes the chemotactic field enabling T cell transit.

    Evidence Neutrophil-specific CCR7-deficient chimeras, photoconvertible mouse tracking, S. aureus models; ACKR4-KO mice with intravital microscopy and flow-induced gene expression analysis

    PMID:35108538 PMID:35119939

    Open questions at the time
    • signaling pathway in neutrophils vs. T cells/DCs not compared
    • whether ACKR4 shapes gradients for neutrophil migration as well is unknown
  21. 2023 High

    CCR7's role as both sensor and sink for CCL19 was demonstrated: ligand-induced internalization depletes local CCL19, creating self-generated gradients that drive collective DC migration and long-range guidance; in cancer, CCR7-PI3Kγ signaling was shown to confer ALK-inhibitor resistance and CNS dissemination in ALCL.

    Evidence Chemotaxis assays with mathematical modeling and gradient visualization; ALCL patient-derived xenografts, CCR7 genetic deletion, PI3Kγ/δ inhibitor duvelisib, constitutively active PI3Kγ model

    PMID:37379367 PMID:37656776

    Open questions at the time
    • self-generated gradient mechanism not validated for CCL21
    • whether PI3Kγ dependence applies broadly to CCR7-driven cancers beyond ALCL is untested
    • structural basis of CCR7–PI3Kγ coupling not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CCR7 homodimerization and ligand-selective internalization, the full phosphorylation code on CCR7's C-terminus that differentiates β-arrestin vs. G-protein outcomes, and whether therapeutic CCR7 antagonism can selectively block pathological (cancer/leukemia) migration without disrupting homeostatic immune cell trafficking.
  • no high-resolution structure of CCR7 in complex with either ligand
  • phosphosite-specific mutagenesis linking C-tail phosphorylation to distinct signaling arms not performed
  • selective therapeutic targeting strategy not demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 5 GO:0005768 endosome 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2
Partners
ACKR4ARRB1CCL19CCL21FOXO1RAC1SRCVAV1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CCL19 (ELC) was identified as a specific, high-affinity functional ligand for CCR7 (EBI1): recombinant ELC-alkaline phosphatase fusion protein bound specifically to CCR7-transfected cells, and ELC induced calcium mobilization and chemotaxis exclusively through CCR7 among five CC chemokine receptors and five orphan receptors tested. Receptor-binding assay with alkaline phosphatase-fused ligand, calcium mobilization assay, chemotaxis assay in stably transfected cells The Journal of biological chemistry High 9153236
1998 CCR7-mediated chemotaxis in lymphocytes is coupled to a Gαi protein, as demonstrated by complete blockade with pertussis toxin; CCL19 (CK beta-11/MIP-3β/ELC) induced actin polymerization and calcium mobilization in T and B cells via CCR7. Chemotaxis assay with pertussis toxin inhibition, actin polymerization assay, calcium mobilization assay Journal of immunology High 9498785
1995 CCR7 (BLR2/EBI1) gene transcription is specifically induced by Epstein-Barr virus nuclear antigen 2 (EBNA2) in B cells, identifying EBNA2 as a transcriptional activator of CCR7. Northern blot, estrogen-inducible EBNA2 activation system in EBV-negative BL41 cells Biochemical and biophysical research communications Medium 7488016
2001 CCL19 (ELC) and CCL21 (SLC) differ fundamentally in their ability to induce CCR7 internalization: CCL19 rapidly induces CCR7 internalization and receptor desensitization in a time- and concentration-dependent manner, whereas CCL21 does not trigger internalization, allowing persistent CCR7 surface expression and continued responsiveness. Flow cytometry-based receptor redistribution assay, functional desensitization assay in CCR7-bearing T lymphocytes European journal of immunology High 11745346
2002 CCR7 mediates lymphocyte homing to peripheral lymph nodes through a JAK tyrosine kinase-dependent pathway: the JAK inhibitor Tyrphostin AG490 blocked CCR7-mediated chemotaxis and CCL21-induced α4/β2 integrin upregulation, and CCL21 stimulation induced rapid Jak2 phosphorylation in primary mouse lymphocytes; in vivo, AG490-treated lymphocytes showed significantly reduced adhesion in high endothelial venules. Pharmacological inhibition (Tyrphostin AG490), static and flow adhesion assays, intravital microscopy, Jak2 phosphorylation by western blot Blood High 12393730
2003 CCR7-mediated T lymphocyte polarization and chemotaxis require Rho kinase: inhibition of Rho kinase isoforms with Y-27632 strongly blocked CCL19- and CCL21-induced polarized morphology and chemotaxis, whereas blockade of ERK2 had no effect on these processes. Pharmacological inhibition (Y-27632 for Rho kinase; ERK inhibitor), T lymphocyte chemotaxis and polarization assays FEBS letters Medium 12729902
2004 CCR7 is essential for dendritic cell entry into dermal lymphatic vessels and for DC migration to skin-draining lymph nodes under both inflammatory and steady-state conditions; CCR7-deficient mice lacked a population of semimature tolerogenic DCs in skin-draining lymph nodes. CCR7 knockout mouse model, flow cytometry, immunohistology, DC trafficking assays Immunity High 15308107
2004 CCR7 signaling regulates the migration of early T cell progenitors from the cortico-medullary junction toward the outer thymic cortex; CCR7-deficient mice show disturbed thymic architecture, impaired T cell development, and accumulation of CD25+CD44+ cells at the cortico-medullary junction. CCR7 knockout mouse model, immunohistology, mixed bone marrow chimeras, flow cytometry The Journal of experimental medicine High 15302903
2007 CCR7 signaling inhibits T cell proliferation and IL-2 secretion: sustained engagement of CCR7 by high concentrations of soluble or immobilized CCL19/CCL21 induces cell cycle arrest associated with delayed degradation of the CDK inhibitor p27Kip1 and downregulation of CDK1; CCR7 knockout T cells show increased proliferative responses, confirming receptor specificity. T cell proliferation assays with soluble/immobilized ligand, CCR7 KO comparison, western blot for p27Kip1 and CDK1 Journal of immunology High 17982037
2008 CCR7 in vivo surface expression and occupancy are dynamically modulated by its ligands: in secondary lymphoid organs (but not blood), most T cell CCR7 is occupied by CCL19, leading to continuous signaling and reduced ligand sensitivity; both ligands trigger CCR7 internalization in vivo as shown in Ccl19-deficient and plt/plt mice. In vivo CCR7 occupancy analysis, Ccl19-/- and plt/plt mice, in vitro internalization assays Journal of immunology High 19017956
2009 CCR7 expression in T-ALL is transcriptionally controlled by the Notch1 oncogene; CCR7 (and its ligand CCL19) is the essential signal required for leukaemic T-cell infiltration of the CNS—silencing either CCR7 or CCL19 specifically inhibits CNS infiltration in a mouse T-ALL model. Gene expression profiling, T-ALL animal modeling, CCR7/CCL19 silencing (genetic), xenograft with human T-ALL cells Nature High 19536265
2009 CCR7 controls lymphocyte egress from body cavities: CCR7 deficiency causes massive accumulation of CD4+, CD8+ T cells and B-2 B cells in the peritoneal and pleural cavities due to impaired CCR7-dependent lymphocyte exit, not altered maturation status. CCR7 knockout mouse model, flow cytometry of peritoneal/pleural lavage cells, lymphocyte recirculation assays Journal of leukocyte biology Medium 20028772
2010 The actin-bundling protein L-plastin (LPL) is required for CCR7-mediated T cell motility: LPL-deficient T cells fail to polarize CCR7 to the leading edge upon CCR7 ligation, resulting in defective chemotaxis and reduced thymic egress in vivo; however, CCR7 signaling to F-actin polymerization and CCR7-mediated costimulation remain intact in LPL-/- cells. LPL knockout mice, two-photon microscopy of lymph nodes, intravital migration assays, receptor localization imaging, thymic egress assays Journal of immunology High 20194718
2012 CCR7/CCL19 signaling upregulates EDG-1 (S1P1) expression in T cells via an ERK5–KLF-2 signaling axis: CCL19 stimulation induces ERK5 phosphorylation and increased expression of the transcription factor KLF-2 and subsequently EDG-1, which mediates T cell egress from lymph nodes; ERK5 deletion in T cells (Lck-Cre) abolishes this CCL19-induced EDG-1 upregulation. T cell stimulation assays, ERK5-flox/Lck-Cre conditional KO mice, migration assays to S1P ligands, western blot The Journal of biological chemistry High 22334704
2014 CCR7 uses distinct, largely independent signaling modules in dendritic cells with biased functionality: PI3K/Akt controls DC survival, the MAPK pathway controls chemotaxis, and the RhoA pathway controls actin dynamics, migratory speed, cytoarchitecture, and endocytosis. Pharmacological inhibition of individual signaling pathways, DC functional assays (survival, chemotaxis, speed, endocytosis), biochemical pathway analysis Frontiers in immunology Medium 32351499
2015 CCR7 is N-glycosylated at two specific residues in the N-terminus and third extracellular loop; glycosylation (particularly sialylation) dampens CCR7 signaling and receptor endocytosis, thereby restraining chemotactic responses. Dendritic cells boost T cell migration by secreting deglycosylating enzymes that remove sialylation from CCR7 on T cells, and also proteolytically convert immobilized CCL21 to a soluble form with distinct signaling properties. Mutagenesis of glycosylation sites, enzymatic deglycosylation, flow cytometry, migration assays, receptor endocytosis assays; metabolic glycan labeling Journal of leukocyte biology High 26819318
2015 CCL19 NMR solution structure reveals a canonical chemokine fold; chemical shift mapping shows that the N-termini of PSGL-1 and CCR7 have overlapping, competitive binding sites for CCL19, providing a structural basis for PSGL-1 enhancement of T cell recruitment. NMR solution structure determination, chemical shift perturbation mapping, competitive binding assay Biochemistry High 26115234
2015 CCR7 expression on breast cancer cells promotes tumor lymphangiogenesis via VEGF-C secretion through the AKT signaling pathway: CCR7-mediated AKT activation drives VEGF-C secretion, which promotes lymphatic endothelial cell proliferation, migration, and tube formation. CCR7/CCL21 gene-manipulated orthotopic xenograft mouse model, in vitro lymphangiogenesis assays (proliferation, migration, tube formation), AKT inhibition, ELISA Molecular cancer Medium 25744065
2017 CCR7 homodimerization directly regulates CCR7-dependent cell migration and signaling: induction of stable CCR7 homodimers enhanced cell migration and CCL19 binding, while a novel CCR7-derived synthetic peptide that disrupted homodimerization attenuated CCR7-dependent migration, ligand-induced internalization, actin rearrangement, and Akt/Erk signaling. CCR7 homodimer induction/disruption (synthetic peptide), CXCR4/CCR7 heterodimerization experiments, migration assays, ligand-binding assays, internalization assays, signaling (Akt/Erk) western blot Scientific reports High 28819198
2018 Glycolytic metabolism is required for CCR7 oligomerization and DC migration to draining lymph nodes: early glycolysis induction (via AKT, TBK, mTOR activation) supports elongated DC morphology, CCR7 oligomerization on the cell surface, and DC motility; inhibiting glycolysis impairs these functions regardless of mitochondrial bioenergetics. Glycolysis inhibition (2-DG), AKT/TBK/mTOR pathway analysis, CCR7 oligomerization assays, DC motility assays, in vivo DC migration to lymph nodes Nature communications High 29941886
2019 CCR7 stimulation activates the HIF-1α transcription factor pathway in DCs, inducing metabolic reprogramming toward glycolysis to fuel DC migration; CCR7 stimulation also upregulates the lncRNA lnc-Dpf3 by removing m6A methylation to prevent RNA degradation. lnc-Dpf3 then directly binds HIF-1α and suppresses HIF-1α-dependent transcription of the glycolytic gene Ldha, creating a negative feedback loop that restrains CCR7-mediated DC migration. DC-specific lnc-Dpf3 knockout, RNA pull-down/RIP for lnc-Dpf3:HIF-1α interaction, m6A modification analysis, metabolic (glycolysis) assays, in vivo DC migration assays, inflammatory disease models Immunity High 30824325
2019 CCR7 signals from endomembrane compartments to sustain directed DC migration: upon CCL19 binding, β-arrestin and Src kinase are co-trafficked with internalized CCR7 to endosomes; Src tyrosine-phosphorylates CCR7 at endomembranes, recruiting Vav1 (a RhoGEF) and Rac1 to form a multi-protein signaling complex; photoactivation of Rac1 at endomembranes drives lamellipodia formation at the leading edge. Co-immunoprecipitation, proximity ligation assay, vesicular trafficking inhibition, Src kinase mutagenesis, Rac1 photoactivation, live-cell imaging Cell reports High 31644919
2020 CCL21/CCR7 axis promotes EMT and cancer stemness in OSCC via JAK2/STAT3 pathway: CCL21 stimulation markedly increased phospho-JAK2 and phospho-STAT3; JAK2/STAT3 inhibition suppressed CCL21-induced EMT and stemness markers; CCR7 knockdown blocked these effects. CCR7 knockdown/overexpression, JAK2/STAT3 inhibitor treatment, western blot for EMT and stemness markers, migration/invasion/tumorsphere assays Journal of cellular physiology Medium 32017846
2021 At CCR7, CCL19 and CCL21 both stimulate G protein signaling and β-arrestin recruitment, with CCL19 consistently displaying higher potency; this systematic comparison in the same cellular background reveals CCR7's intrinsic coupling capabilities without evidence of ligand-biased agonism between CCL19 and CCL21. Systematic BRET-based G protein activation and β-arrestin recruitment assays in a uniform cellular background International journal of molecular sciences Medium 33921794
2022 Neutrophils upregulate CCR7 in response to microbial stimuli and migrate from inflamed skin to draining lymph nodes via lymphatic vessels in a CCR7-dependent manner; in the lymph nodes, these neutrophils are phagocytosed by resident cDC1 and cDC2, and CCR7-deficient neutrophils show increased antistaphylococcal immunity and aggravated skin inflammation. Selective CCR7 deficiency on neutrophils (bone marrow chimeras), photoconvertible mouse tracking, mouse models of TLR-induced skin inflammation and S. aureus infection, flow cytometry Science immunology High 35119939
2022 ACKR4 (atypical chemokine receptor 4) expressed on lymphatic collector endothelium acts as a flow-induced scavenger of CCL19 and CCL21, enabling T cell detachment from the vessel wall and transition to free-flow transport toward draining lymph nodes; loss of ACKR4 causes T cell accumulation in dermal collecting vessel segments. ACKR4-deficient mice, flow-induced gene expression analysis, T cell trafficking assays in TPA-induced inflammation, intravital microscopy Cell reports High 35108538
2023 CCR7 acts as both a sensor and a sink for CCL19: upon CCL19 binding, DCs internalize CCR7 together with CCL19 as part of canonical GPCR desensitization, which depletes the local chemokine and dynamically reshapes the chemotactic gradient. This self-generated gradient mechanism drives collective DC migration, enables long-range guidance, and allows DCs to guide comigrating cells. Experimental chemotaxis assays combined with mathematical modeling, CCR7 internalization tracking, chemokine gradient visualization, collective migration assays Science immunology High 37656776
2014 Epigenetic silencing of the Ccr7 locus by H3K27me3 (trimethylation of histone 3 lysine 27) controls differential CCR7 expression between conventional DCs and monocyte-derived DCs in the lung, and this epigenetic modification is acquired gradually during monocyte-to-moDC differentiation rather than at early lineage commitment. ChIP-seq/ChIP-PCR for H3K27me3, comparison of bone marrow-derived and lung DC subsets, monocyte differentiation time-course Journal of immunology Medium 25297875
2015 FOXO1 directly binds the CCR7 promoter and stimulates CCR7 transcriptional activity in dendritic cells; FOXO1 nuclear localization is induced by bacteria through the MAPK pathway, and FOXO1-dependent CCR7 expression is required for DC chemotaxis and lymph node homing in vivo. ChIP assay for FOXO1 binding at CCR7 promoter, luciferase reporter assay, DC-specific FOXO1 KO (CD11c.Cre), ICAM-1/CCR7 rescue transfection, in vivo lymph node homing assay Journal of immunology High 25786691
2013 CCL19/CCR7 promotes invasion of lung cancer cells by upregulating heparanase via the transcription factor Sp1: CCL19 stimulation increased Sp1 and heparanase expression; CCR7 blockade suppressed Sp1 and heparanase; Sp1 inhibition downregulated heparanase; and ChIP demonstrated Sp1 binding to the heparanase promoter. CCR7 blocking antibody, Sp1 inhibition, ChIP for Sp1 binding to heparanase promoter, RT-PCR, western blot, cell invasion assay Tumour biology Medium 23649655
2009 JAK3 participates in CCR7-mediated DC migration: Jak3-/- bone marrow-derived DCs show impaired chemotactic responses to CCL19 and CCL21 in vitro and in vivo, reduced co-stimulatory molecule expression, and decreased ability to activate T lymphocytes. Jak3 knockout mice, in vitro and in vivo DC migration assays (CCL19/CCL21), contact hypersensitivity assay, lymphocyte proliferation assay PloS one Medium 19759904
2023 CCR7 activates PI3Kγ in ALCL tumor cells, providing a survival pathway that confers resistance to ALK tyrosine kinase inhibitors; endothelial cells producing CCL19/CCL21 protect ALCL cells from apoptosis in a CCR7-dependent manner, and genetic CCR7 deletion blocks CNS dissemination and perivascular growth of ALCL in TKI-treated mice. ALCL cell lines and patient-derived xenografts, 3D microfluidic chip with endothelial cells, CCR7 genetic deletion in mouse models, PI3Kγ/δ inhibitor (duvelisib), constitutively active PI3Kγ mouse model Science translational medicine High 37379367
2018 CCR7 signals through the PI3K/Akt pathway to support DC and cancer cell survival, through MAPK to control chemotaxis, and through RhoA to regulate actin dynamics; these pathways function as biased, largely independent modules for distinct cellular functions. Pathway-specific pharmacological inhibitors, DC functional assays (survival, chemotaxis, endocytosis, actin dynamics), biochemical signaling analysis Frontiers in pharmacology (review synthesizing primary data) Medium 35281921

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 1140 18379575
2004 CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 800 15308107
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 323 9153236
2013 CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets. The Journal of experimental medicine 318 24378538
2019 CCR7 Chemokine Receptor-Inducible lnc-Dpf3 Restrains Dendritic Cell Migration by Inhibiting HIF-1α-Mediated Glycolysis. Immunity 293 30824325
2002 Expression of chemokine receptor CCR7 is associated with lymph node metastasis of gastric carcinoma. Cancer research 266 12019175
2005 IL-18-induced CD83+CCR7+ NK helper cells. The Journal of experimental medicine 235 16203865
2009 CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia. Nature 222 19536265
2002 The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes. Blood 175 11929789
2018 Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration. Nature communications 172 29941886
2005 Stepwise differentiation of CD4 memory T cells defined by expression of CCR7 and CD27. Journal of immunology (Baltimore, Md. : 1950) 159 16272303
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 150 15073111
2003 Cooperating mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs. The Journal of experimental medicine 136 12732661
2015 The role of CCL21/CCR7 chemokine axis in breast cancer-induced lymphangiogenesis. Molecular cancer 115 25744065
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