Affinage

XCR1

Chemokine XC receptor 1 · UniProt P46094

Length
333 aa
Mass
38.5 kDa
Annotated
2026-06-11
87 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

XCR1 (formerly GPR5) is a Gαi-coupled chemokine receptor that binds the C-class chemokine XCL1 (lymphotactin/SCM-1) as its specific high-affinity ligand to drive chemotaxis and intracellular Ca2+ mobilization, with signaling abolished by pertussis toxin (PMID:9632725). Receptor activation requires the native XCL1 N-terminus presented in the canonical Ltn10 chemokine fold; the XCL1 C-terminal extension is dispensable for binding and activation (PMID:17302442, PMID:30619244), and N-terminal residues Val1–Glu4 supply most of the binding energy, with XCL1 Glu4 contacting XCR1 Tyr117 and Arg273 to trigger Gi signaling (PMID:31481523). A cryo-EM structure of human XCR1–Gi bound to engineered XCL1 confirms that the XCL1 N-terminal segment inserts into the orthosteric pocket and that the unique binding-site arrangement confers ligand specificity (PMID:39565315). XCR1 undergoes constitutive, ligand-enhanced internalization that is independent of β-arrestin 1 and 2 (PMID:31649144). Functionally, XCR1 marks the cross-presenting conventional type 1 dendritic cell (cDC1) lineage: it is selectively expressed on murine CD8α+/CD103+ DCs and human CD141+/BDCA3+ DCs, depends on Batf3 and Flt3L, and identifies terminally differentiated, effector-competent cDC1 (PMID:19913446, PMID:20479115, PMID:21948982, PMID:22826713, PMID:37566635). Activated CD8+ T cells and NK cells secrete XCL1 to recruit XCR1+ cDC1s to sites of T cell priming, forming a feedforward loop that optimizes antigen cross-presentation, cytotoxic and memory CD8+ T cell immunity, and tissue-resident memory T cell programming (PMID:19913446, PMID:28190711, PMID:26694969, PMID:39841133); this axis is exploited therapeutically by targeting antigens to XCR1 for potent CD8+ T cell responses (PMID:25520399, PMID:25410055). Beyond immunity, XCR1 is functionally expressed on epithelial cells, trophoblasts, and neurons, where XCL1 engages ERK, PI3K/AKT, and MMP-2/MMP-9 pathways to modulate cell migration/invasion and nociceptive signaling (PMID:20225245, PMID:29856101, PMID:29588250, PMID:36618360). The viral chemokine vMIP-II antagonizes XCR1 (PMID:10679309), and cytomegalovirus-encoded vXCL1 hijacks the axis to selectively engage XCR1+ DCs (PMID:24155383, PMID:31649144).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1998 High

    Established the molecular identity of the orphan receptor GPR5 by showing it is the specific Gαi-coupled receptor for the C-class chemokine XCL1, defining the XCL1–XCR1 ligand-receptor pair.

    Evidence Stable expression in L1.2 cells with chemotaxis, Ca2+ flux, radioligand binding, and pertussis toxin treatment

    PMID:9632725

    Open questions at the time
    • Did not resolve the structural basis of ligand recognition
    • No physiological cell-type expression context
  2. 2000 Medium

    Identified a pharmacological antagonist (viral vMIP-II) of XCR1, providing a tool to block the receptor and extending viral chemokine mimicry to the C-class.

    Evidence Cell-based antagonism assay in GPR5/XCR1-expressing cells

    PMID:10679309

    Open questions at the time
    • Binding mode of antagonism not determined
    • Single method/single lab
  3. 2001 Low

    Tested whether XCR1 expression extends to neutrophils and B cells beyond T/NK cells, broadening the candidate responder cell pool.

    Evidence RT-PCR and in vitro chemotaxis in mouse hematopoietic populations

    PMID:11181058

    Open questions at the time
    • Low-confidence: RT-PCR-based, not confirmed by later DC-focused work which suggests restricted expression
    • No protein-level or in vivo validation
  4. 2007 High

    Defined which conformation and region of XCL1 is required for receptor activation, showing the Ltn10 chemokine fold and native N-terminus—not the C-terminal extension—drive XCR1 agonism.

    Evidence NMR characterization of disulfide-locked XCL1 mutants with Ca2+ flux in XCR1-expressing cells

    PMID:17302442

    Open questions at the time
    • Receptor-side contact residues not yet mapped
    • No structure of the complex
  5. 2009 High

    Determined that XCR1 is exclusively expressed on murine CD8+ cross-presenting DCs and that the T cell-derived XCL1–XCR1 axis is required for cytotoxic CD8+ T cell immunity in vivo.

    Evidence Flow cytometry, in vivo chemotaxis, XCL1-deficient mice, antigen-specific cytotoxicity

    PMID:19913446

    Open questions at the time
    • Human relevance not yet shown
    • Kinetics of receptor signaling in vivo undefined
  6. 2010 High

    Extended the XCR1+ cross-presenting DC paradigm to humans and established conservation of the axis, with human CD141+ DCs as the sole XCR1-responsive blood DC subset.

    Evidence Flow cytometry, Ca2+ and chemotaxis assays, cross-presentation on purified human DCs; parallel mouse NK/DC profiling

    PMID:20479115 PMID:20541533

    Open questions at the time
    • In vivo functional requirement in humans not testable
    • Mechanism of cross-presentation enhancement unresolved
  7. 2010 Medium

    Revealed XCR1 signaling competence outside the immune system on epithelial/carcinoma cells, linking XCL1–XCR1 to ERK activation, migration/invasion, and MMP release.

    Evidence RT-PCR, surface flow cytometry, ERK phosphorylation, migration/invasion/MMP zymography in keratinocytes and OSCC lines

    PMID:20225245

    Open questions at the time
    • G-protein coupling in these cells not dissected
    • Single lab, no in vivo confirmation
  8. 2011 High

    Showed XCR1 marks a single transcriptionally defined DC lineage spanning lymphoid CD8α+ and non-lymphoid CD103+ DCs across tissues, unifying the cross-presenting subset.

    Evidence Flow cytometry, gene expression profiling, anti-XCR1 staining across multiple tissues

    PMID:21948982

    Open questions at the time
    • Functional differences between tissue subsets not resolved
    • Developmental dependency not yet defined
  9. 2012 High

    Placed XCR1 genetically downstream of Batf3 and Flt3L and confirmed XCR1+ DCs are the cells that uptake cellular material and excel at cross-presentation, establishing XCR1 as a definitive lineage marker.

    Evidence Custom anti-XCR1 mAb, Batf3-KO and Flt3L-KO mice, cross-presentation assays

    PMID:22826713

    Open questions at the time
    • Whether XCR1 signaling (vs marker status) is required for cross-presentation not separated
  10. 2013 High

    Used genetic ablation of XCR1+ DCs to show they are specifically required for CD8+ T cell responses to viral/dsRNA and bacterial challenge while sparing CD4+ responses.

    Evidence XCR1-venus and XCR1-DTRvenus knock-in mice, diphtheria toxin depletion, infection models

    PMID:23670193

    Open questions at the time
    • Distinguishes DC-population role, not the receptor's signaling contribution per se
  11. 2013 Medium

    Showed that cytomegalovirus has evolved a viral XCL1 mimic (vXCL1) that selectively engages XCR1+ DCs, indicating pathogen subversion of the axis.

    Evidence Recombinant vXCL1 binding and chemotaxis assays on primary rat DCs

    PMID:24155383

    Open questions at the time
    • Whether vXCL1 acts as agonist or decoy in vivo not resolved
    • Single lab
  12. 2014 High

    Demonstrated XCR1 as a vaccine target, with XCL1- or anti-XCR1-vectored antigens driving potent CD8+ cytotoxicity and tumor protection, validated by XCR1-KO and human-XCR1 transgenic specificity controls.

    Evidence XCR1-KO and human XCR1 transgenic mice, in vivo antigen targeting, cytotoxicity and tumor protection; bivalent Xcl1 DNA vaccines with influenza challenge

    PMID:25410055 PMID:25520399

    Open questions at the time
    • Optimal valency/affinity for delivery not systematized
    • Humoral vs cellular balance not yet explained
  13. 2015 High

    Extended XCR1+ DC requirement to memory CD8+ T cell recall and dissected the effector program (IL-12, CXCL9, CXCR3-dependent CTL attraction, NK cooperation), with pathogen-specific dependency.

    Evidence Conditional XCR1+ DC depletion, intravital imaging, cytokine/chemokine neutralization across Listeria, VSV, Vaccinia, MCMV

    PMID:26694969

    Open questions at the time
    • Why MCMV recall is XCR1-DC-independent unexplained
  14. 2016 Medium

    Identified a neuronal XCR1 role in pathological pain, where spinal XCR1 is microglia-driven and intrathecal XCL1 enhances nociception, with neutralization relieving allodynia.

    Evidence Western blot, immunofluorescence, intrathecal XCL1, behavioral pain tests, microglial cultures (diabetic neuropathy model)

    PMID:27387353

    Open questions at the time
    • Direct receptor-level signaling in neurons not dissected here
    • Single lab
  15. 2016 High

    Showed the XCL1–XCR1 axis maintains intestinal T cell populations and DC positioning, revealing a mucosal homeostatic function.

    Evidence XCR1-KO and XCL1-KO mice with concordant phenotypes, flow cytometry, transcriptome, colitis model

    PMID:27005831

    Open questions at the time
    • Mechanism by which XCR1+ DCs support T cell survival undefined
  16. 2017 High

    Defined a feedforward priming loop in which activated CD8+ T cells recruit XCR1+ DCs via XCL1 to enable pDC–cDC1 cooperation and optimal cross-presentation.

    Evidence Intravital lymph node imaging, CCR5-KO mice, XCL1 blockade

    PMID:28190711

    Open questions at the time
    • Quantitative XCL1 gradient dynamics not measured
  17. 2017 Medium

    Revealed that human vs murine XCL1 differ in inducing XCR1 chemotaxis/endocytosis, linking receptor internalization efficiency to the humoral-vs-cellular immunity balance.

    Evidence Comparative binding, chemotaxis, endocytosis assays and in vivo immunization/influenza challenge

    PMID:28228559

    Open questions at the time
    • Structural basis of species-specific endocytosis difference unknown
    • Single lab
  18. 2018 High

    Mapped XCL1 N-terminal residues (Val1–Glu4) as stabilizing/activating elements for XCR1 while showing the C-terminus is dispensable for binding, chemotaxis, and in vivo antigen handling.

    Evidence Systematic XCL1 deletion mutants in binding and in vivo CD8+ proliferation/cytotoxicity assays

    PMID:30619244

    Open questions at the time
    • Receptor-side counterpart residues addressed only later
    • Paradoxical concentration-dependent chemotaxis limit unexplained
  19. 2018 Medium

    Extended XCR1 signaling to trophoblast invasion and neuronal nociception, identifying PI3K/AKT/MEK/JNK and ERK/p38/c-Fos as effector pathways modulated by XCL1.

    Evidence Invasion/wound-healing assays with MMP zymography and pathway inhibitors (trophoblast); electrophysiology and signaling assays with vMIP-II antagonism (trigeminal neurons)

    PMID:29588250 PMID:29856101

    Open questions at the time
    • Whether these are Gi-dependent like immune signaling not tested
    • Single labs
  20. 2019 High

    Identified specific receptor contact residues (XCR1 Tyr117, Arg273 engaging XCL1 Glu4) and dissected the Gi signaling and β-arrestin-independent internalization mechanism of XCR1.

    Evidence Rosetta modeling with ligand/receptor mutagenesis, IP3/Ca2+/migration assays; HEK293A and primary DCs with β-arrestin-KO internalization assays and species-specific vXCL1 signaling

    PMID:31481523 PMID:31649144

    Open questions at the time
    • Pre-cryo-EM: full atomic complex not yet solved
    • Adaptor mediating β-arrestin-independent internalization unidentified
  21. 2021 High

    Demonstrated a pathogenic role for the XCR1+ cDC1–XCL1 axis in NASH, where these DCs drive inflammatory T cell reprogramming and disease.

    Evidence XCR1-DTA depletion and anti-XCL1 blockade in NASH models, single-cell and paired DC–T cell sequencing

    PMID:34017133

    Open questions at the time
    • Direct receptor-signaling requirement (vs DC depletion) not isolated
  22. 2023 High

    Established that acquisition of XCR1 marks the terminal differentiation step of fully functional human cDC1 with effector cytokine, NK-activating, and antiviral capacity.

    Evidence Flow cytometry, cytokine assays, NK co-culture, influenza replication, in vitro DC differentiation tracking

    PMID:37566635

    Open questions at the time
    • Signals controlling XCR1 induction during differentiation unresolved
  23. 2024 High

    Solved the cryo-EM structure of human XCR1–Gi with engineered XCL1, providing the definitive structural mechanism of N-terminal insertion, specificity, and activation.

    Evidence Cryo-EM with site-directed mutagenesis validation

    PMID:39565315

    Open questions at the time
    • Inactive-state and antagonist-bound structures not determined
    • Internalization machinery not structurally addressed
  24. 2024 Medium

    Identified a transcriptional regulatory mechanism (RUNX2 phase separation linking a GWAS enhancer SNP to the XCR1 locus) controlling XCR1 expression in osteoblast differentiation and bone formation.

    Evidence CRISPR editing, chromatin conformation capture, phase separation assays, AAV-Xcr1 delivery in osteoporosis mice

    PMID:39704037

    Open questions at the time
    • Downstream XCR1 signaling in osteoblasts not characterized
    • Single lab
  25. 2025 High

    Showed the XCL1–XCR1 axis non-cell-autonomously programs intestinal CD8+ TRM differentiation and spatial positioning, with enforced XCL1 boosting intratumoral cDC1 and T cell persistence and survival.

    Evidence Murine genetic models, spatial transcriptomics, tumor and infection models, human TIL/TRM validation

    PMID:39841133

    Open questions at the time
    • Spatial signaling cues coordinating TRM positioning incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How XCR1's β-arrestin-independent constitutive internalization is mechanistically achieved, and whether non-immune (neuronal, epithelial, trophoblast, osteoblast) XCR1 signaling uses the same Gi pathway as cDC1s, remains unresolved.
  • Internalization adaptor unidentified
  • Cell-type-specific G-protein/effector coupling not compared head-to-head
  • Inactive-state structure lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 4
Partners
XCL1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 GPR5 (renamed XCR1) was identified as the specific receptor for SCM-1α/SCM-1β (lymphotactin/XCL1). Both proteins induced chemotaxis and intracellular calcium mobilization in L1.2 cells stably expressing GPR5; migration was suppressed by pertussis toxin, indicating coupling to a Gαi-type G protein. SCM-1α bound specifically to GPR5-expressing cells with a Kd of 10 nM. Stable expression in L1.2 cells, chemotaxis assay, calcium mobilization assay, radioligand binding, pertussis toxin treatment The Journal of biological chemistry High 9632725
2000 Viral macrophage inflammatory protein-II (vMIP-II) was identified as a potent antagonist of lymphotactin activity at GPR5/XCR1, extending the known range of chemokine classes inhibited by this viral protein to include C-class chemokines. Cell-based antagonism assay using GPR5/XCR1-expressing cells Biochemical and biophysical research communications Medium 10679309
2001 Mouse neutrophils and B cells express XCR1 and chemotactically respond to lymphotactin (XCL1) in vitro, extending known XCR1 expression beyond T and NK cells to these additional hematopoietic populations. RT-PCR for XCR1 expression, in vitro chemotaxis assay Biochemical and biophysical research communications Low 11181058
2007 The canonical chemokine fold of XCL1 (Ltn10 conformation) is responsible for XCR1 receptor activation. An engineered second disulfide bond that locks XCL1 in the Ltn10 conformation retained full XCR1 agonist activity (Ca2+ flux), whereas the C-terminal 25-residue extension does not participate in receptor activation; the native N-terminus is absolutely required for XCR1 activation. NMR structural characterization of XCL1 mutants, intracellular Ca2+ flux assay in XCR1-expressing cells Biochemistry High 17302442
2009 XCR1 is exclusively expressed on murine CD8+ dendritic cells and mediates highly specific chemotaxis toward XCL1. CD8+ T cells secrete XCL1 8–36 hours after antigen recognition on CD8+ DCs in vivo; the XCL1-XCR1 axis is required for efficient development of cytotoxic CD8+ T cell immunity and cross-presentation-dependent immune responses. Flow cytometry, in vivo chemotaxis assay, XCL1-deficient mice, antigen-specific cytotoxicity assays Immunity High 19913446
2010 Human CD141+ (BDCA3+) DCs are the only cells in human blood expressing XCR1 and respond to XCL1 by Ca2+ mobilization and potent chemotaxis. These cells are homologues of mouse CD8+ DCs and excel in cross-presentation of soluble and cell-associated antigen to CD8+ T cells. Flow cytometry, Ca2+ mobilization assay, chemotaxis assay, antigen cross-presentation assay with purified DC subsets The Journal of experimental medicine High 20479115
2010 Murine XCR1 is the only chemokine receptor selectively expressed in CD8α+ conventional DCs, and XCL1 is constitutively expressed by NK cells; expression patterns of the XCL1-XCR1 axis are conserved between mice and humans (including BDCA3+ DCs). Flow cytometry, RT-PCR, NK cell activation assays, XCL1 ELISA Biochemical and biophysical research communications Medium 20541533
2011 XCR1 expression defines both lymphoid tissue-resident CD8α+ DCs and non-lymphoid tissue-derived CD103+ DCs as a common DC subset throughout the body, characterized by a unique transcriptional fingerprint irrespective of tissue of origin. Flow cytometry, gene expression profiling, anti-XCR1 antibody staining across multiple tissues Journal of immunology High 21948982
2012 Using an anti-XCR1 monoclonal antibody, only XCR1+CD8+ DCs (and their probable XCR1+CD8− precursors) efficiently take up cellular material and excel in antigen cross-presentation. XCR1+ DCs throughout spleen, lymph nodes, and peripheral tissues are dependent on Flt3 ligand and selectively absent in Batf3-deficient animals, establishing XCR1 as a lineage marker for the Batf3-dependent cross-presenting DC subset. Anti-XCR1 mAb generation, flow cytometry, antigen cross-presentation assay, Batf3-deficient and Flt3L-deficient mouse models Frontiers in immunology High 22826713
2013 XCR1-expressing DCs (identified via XCR1-venus knock-in mice) are required for CD8+ T cell responses to dsRNA stimuli and Listeria monocytogenes infection. XCR1+ DCs are selectively ablated by diphtheria toxin in XCR1-DTRvenus mice; depletion impairs CD8+ T cell responses while retaining cytokine and augmenting CD4+ T cell responses. Knock-in mouse model (XCR1-venus, XCR1-DTRvenus), diphtheria toxin depletion, infection model, flow cytometry Journal of immunology High 23670193
2013 Rat cytomegalovirus encodes a viral XCL1 homolog (vXCL1) that exclusively binds to XCR1-expressing CD4− rat DCs and selectively chemoattracts these XCR1+ DCs, demonstrating that the virus has hijacked the XCL1-XCR1 axis to potentially subvert cytotoxic immune responses. Recombinant vXCL1 production, binding assay, in vitro chemotaxis assay, flow cytometry Journal of virology Medium 24155383
2014 Targeting antigens to XCR1 using XCL1 as a vector or anti-XCR1 mAb induces potent CD8+ T cell cytotoxicity in vivo. The specificity of delivery was confirmed using XCR1-deficient mice. A transgenic mouse expressing human XCR1 exclusively on cross-presenting DCs demonstrated that human XCL1-mediated antigen targeting to XCR1 is fully effective in vivo. XCR1-deficient mice, human XCR1 transgenic mice, in vivo antigen targeting, CD8+ T cell cytotoxicity assay, tumor protection assay Journal of immunology High 25520399
2014 Bivalent Xcl1 fused to model antigens specifically bound CD8α+ DCs via XCR1, increased antigen-specific T cell proliferation, and DNA vaccines encoding dimeric XCL1-hemagglutinin fusion proteins induced cytotoxic CD8+ T cell responses and Th1/IgG2a responses, providing full protection against lethal influenza A challenge. Binding assay, T cell proliferation assay, DNA vaccination, lethal influenza challenge model European journal of immunology High 25410055
2016 Mice deficient in XCR1 or its ligand XCL1 have diminished intestinal T cell populations with an accumulation of XCR1+ DCs in the gut, indicating that T cell-derived XCL1 facilitates XCR1+ DC activation and migration in the intestine and that XCR1+ DCs support intestinal T cell survival and function. XCR1-deficient and XCL1-deficient mouse models, flow cytometry, intestinal T cell analysis, colitis model Scientific reports High 27005831
2017 Activated CD8+ T cells recruit XCR1+ DCs to sites of antigen-driven activation via XCL1 secretion. This CD8+ T cell-mediated reorganization allows pDC-XCR1+ DC cooperation, optimizing XCR1+ DC maturation and antigen cross-presentation, demonstrating a feedforward loop in priming. Intravital imaging, CCR5-deficient mice, XCL1-blocking experiments, flow cytometry, lymph node imaging Immunity High 28190711
2018 The N-terminal region of XCL1 (specifically Val1, Gly2, Ser3, Glu4) stabilizes binding to XCR1 and contains critical elements for XCR1 activation, but paradoxically limits chemotactic action at higher concentrations. The C-terminus of XCL1 does not participate in XCR1 receptor binding, chemotaxis, or antigen uptake/presentation in vivo. XCL1 deletion mutant proteins, binding studies with primary XCR1+ DCs, in vivo CD8+ T cell proliferation and cytotoxicity assays Frontiers in immunology High 30619244
2019 Rosetta modeling and structure-function analysis identified that XCL1 N-terminal residues (Val1, Gly2, Ser3, Glu4) contribute the majority of binding energy to XCR1. Residues near Cys11 modulate XCR1 activation. Key receptor contacts include Glu4 of XCL1 interacting with Tyr117 and Arg273 of XCR1; mutagenesis of Tyr117 and Arg273 diminished XCR1 binding and activation. Rosetta computational modeling, mutagenesis of XCL1 and XCR1, IP3 accumulation assay, intracellular Ca2+ release assay, directed cell migration assay Science signaling High 31481523
2019 Rat RCMV-encoded vXCL1 activates XCR1 Gi signaling and induces chemotaxis exclusively in rat XCR1+ DCs in a species-specific manner. XCR1 undergoes constitutive internalization in XCR1-transfected HEK293A cells and in splenic XCR1+ DCs, independent of β-arrestin 1 and 2, and this internalization is enhanced upon vXCL1 and rXCL1 binding. Transfected HEK293A cells, primary splenic XCR1+ DCs, Gi signaling assay, chemotaxis assay, internalization assay, β-arrestin knockout cells Journal of cell science High 31649144
2010 XCR1 is functionally expressed on oral epithelial cells and oral squamous cell carcinoma cell lines; XCL1 activates the ERK1/2 signaling pathway via XCR1 and stimulates migration, invasion, proliferation, and MMP-2/MMP-9 (but not MMP-7) release in normal keratinocytes, with cancer cells showing greater responses including MMP-7 release and increased adhesion to collagen. RT-PCR, flow cytometry for surface XCR1, ERK1/2 phosphorylation assay, migration/invasion/proliferation assays, MMP zymography, adhesion assay The Journal of pathology Medium 20225245
2018 XCL1-XCR1 signaling promotes trophoblast cell migration and invasion by increasing MMP-9 and MMP-2 activity via the PI3K/AKT, MEK, and JNK signaling pathways in human first-trimester placenta. qRT-PCR, wound healing assay, Transwell invasion assay, gelatin zymography for MMP activity, pharmacological pathway inhibition American journal of reproductive immunology Medium 29856101
2018 XCL1-XCR1 axis signaling in trigeminal neurons increases intrinsic excitability and activates c-Fos, ERK and p38 in the superficial layers of trigeminal subnucleus caudalis (Vc); these effects are blocked by the XCR1 antagonist vMIP-II, establishing a role for XCR1 in nociceptive processing. Immunohistochemistry, electrophysiology (brainstem slices), c-Fos/ERK/p38 activation assays, pharmacological antagonism with vMIP-II Neuroscience Medium 29588250
2016 In diabetic neuropathic pain, spinal XCR1 protein is upregulated by microglial activation; XCL1 administered intrathecally enhances nociceptive transmission, and neutralization of XCL1 or inhibition of microglia (which reduces XCR1 levels) alleviates allodynia/hyperalgesia. XCR1-expressing cells co-localize with spinal neurons. Western blot, immunofluorescence, intrathecal drug injection, behavioral pain tests (von Frey, cold plate), primary microglial cell cultures Anesthesiology Medium 27387353
2015 XCR1+ DCs are instrumental for promoting memory CD8+ T cell recall during secondary Listeria monocytogenes, vesicular stomatitis virus, and Vaccinia virus infections, but dispensable for mouse cytomegalovirus secondary challenge. During secondary Listeria infection, XCR1+ DCs produce IL-12 and CXCL9, attract mCTLs in a CXCR3-dependent manner, and cooperate with NK cells to boost recall responses. Conditional depletion mouse model (XCR1+ DC-specific), intravital imaging, in vivo cytokine/chemokine neutralization, CXCR3-blocking experiments The Journal of experimental medicine High 26694969
2024 Cryo-EM structure of human XCR1 in complex with Gi and engineered XCL1 (CC3) reveals the molecular basis for XCL1 binding and XCR1 activation. The N-terminal segment of XCL1 CC3 is vital for XCR1 activation. The unique arrangement of the XCL1 CC3 binding site confers XCL1 specificity. An activation mechanism involving structural alterations of key residues at the bottom of the XCL1 binding pocket is proposed. Cryo-electron microscopy, site-directed mutagenesis, structural analysis Proceedings of the National Academy of Sciences of the United States of America High 39565315
2022 Intrathecal blockade of XCR1 (using vMIP-II antagonist) or neutralization of ITGA9 (the second XCL1 receptor) both reversed XCL1-induced hypersensitivity in naive mice and diminished allodynia/hyperalgesia after nerve injury; ITGA9 neutralization was more effective. XCL1 is released by spinal cord astroglial cells, while its receptors XCR1 and ITGA9 are on neurons. Intrathecal drug injection, behavioral pain tests (von Frey, cold plate), RT-qPCR, Western blot, ELISA, immunofluorescence, CCI neuropathic pain model Frontiers in immunology Medium 36618360
2021 Depletion of XCR1+ cDC1s in XCR1DTA mice or blocking XCL1 (the XCR1 ligand) with anti-XCL1 antibody attenuated liver pathology in NASH mouse models, demonstrating that XCR1+ cDC1s drive inflammatory T cell reprogramming and are essential mediators of NASH pathology. XCR1-DTA conditional depletion mice, anti-XCL1 blocking antibody, NASH mouse models, single-cell transcriptomics, physical DC-T cell pair sequencing Nature medicine High 34017133
2023 Human cDC1 can be subdivided into XCR1− and XCR1+ subsets; XCR1+ cDC1 display a preactivated phenotype, secrete high levels of inflammatory cytokines and chemokines upon stimulation, enhance NK cell activation, and inhibit influenza A virus replication. Under DC differentiation conditions, XCR1− cDC1 develop into XCR1+ cDC1, after which they acquire full effector cytokine secretion capacity, establishing XCR1 as a marker of terminally differentiated, fully functional human cDC1. Flow cytometry, cytokine secretion assays, NK cell co-culture activation assay, influenza virus replication assay, in vitro DC differentiation Proceedings of the National Academy of Sciences of the United States of America High 37566635
2025 The XCL1-XCR1 axis plays a non-cell autonomous role in programming intestinal CD8+ TRM differentiation and spatial positioning; enforced XCL1 expression by antigen-specific CD8+ T cells promoted intratumoral cDC1 accumulation and T cell persistence, improving overall survival in tumor models. Human TIL and TRM also show conserved XCL1/XCL2 expression. Murine genetic models, spatial transcriptomics, tumor models, viral infection models, flow cytometry The Journal of experimental medicine High 39841133
2024 RUNX2 phase separation mediates long-range chromatin interaction between a GWAS enhancer SNP (rs4683184) and the XCR1 gene locus, regulating XCR1 expression and osteoblast differentiation; bone-targeting AAV delivery of Xcr1 improved bone formation in osteoporosis mice. CRISPR editing, chromatin conformation capture, phase separation assays, AAV delivery, osteoblast differentiation assays Advanced science Medium 39704037
2017 Human XCL1 (hXCL1) and hXCL2 fusion vaccines bound cDC1 (XCR1+ DCs) but—unlike murine Xcl1—did not induce chemotaxis and were less efficiently endocytosed, remaining on the DC surface. This difference resulted in enhanced long-term antibody responses with murine cDC1, suggesting that antigen endocytosis efficiency by XCR1 modulates the balance between humoral and cellular immunity. Binding assay, chemotaxis assay, endocytosis assay, in vivo immunization, antibody titer measurement, influenza challenge Journal of immunology Medium 28228559

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. The Journal of experimental medicine 657 20479115
2009 Selective expression of the chemokine receptor XCR1 on cross-presenting dendritic cells determines cooperation with CD8+ T cells. Immunity 361 19913446
2017 CD8+ T Cells Orchestrate pDC-XCR1+ Dendritic Cell Spatial and Functional Cooperativity to Optimize Priming. Immunity 282 28190711
2011 Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8α+ type. Journal of immunology (Baltimore, Md. : 1950) 182 21948982
2021 XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis. Nature medicine 157 34017133
2012 Expression of XCR1 Characterizes the Batf3-Dependent Lineage of Dendritic Cells Capable of Antigen Cross-Presentation. Frontiers in immunology 157 22826713
2011 XCL1 and XCR1 in the immune system. Microbes and infection 153 22100876
2013 Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1. Journal of immunology (Baltimore, Md. : 1950) 146 23670193
1998 Identification of single C motif-1/lymphotactin receptor XCR1. The Journal of biological chemistry 127 9632725
2014 Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 113 25009205
2014 Langerin-expressing dendritic cells in human tissues are related to CD1c+ dendritic cells and distinct from Langerhans cells and CD141high XCR1+ dendritic cells. Journal of leukocyte biology 103 25516751
2012 The Role of XCR1 and its Ligand XCL1 in Antigen Cross-Presentation by Murine and Human Dendritic Cells. Frontiers in immunology 100 22566900
2016 Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. Scientific reports 99 27005831
2014 Vaccine molecules targeting Xcr1 on cross-presenting DCs induce protective CD8+ T-cell responses against influenza virus. European journal of immunology 94 25410055
2015 XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses. The Journal of experimental medicine 91 26694969
2014 Induction of potent CD8 T cell cytotoxicity by specific targeting of antigen to cross-presenting dendritic cells in vivo via murine or human XCR1. Journal of immunology (Baltimore, Md. : 1950) 84 25520399
2015 Laser-assisted intradermal delivery of adjuvant-free vaccines targeting XCR1+ dendritic cells induces potent antitumoral responses. Journal of immunology (Baltimore, Md. : 1950) 70 25941327
2015 Mouse Conventional Dendritic Cells Can be Universally Classified Based on the Mutually Exclusive Expression of XCR1 and SIRPα. Frontiers in immunology 64 25699051
2001 Lymphotactin expression by engineered myeloma cells drives tumor regression: mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor. Journal of immunology (Baltimore, Md. : 1950) 58 11418632
2001 Neutrophils and B cells express XCR1 receptor and chemotactically respond to lymphotactin. Biochemical and biophysical research communications 57 11181058
2011 Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141(+)XCR1+ dendritic cells. Gene therapy 53 22071967
2007 An engineered second disulfide bond restricts lymphotactin/XCL1 to a chemokine-like conformation with XCR1 agonist activity. Biochemistry 53 17302442
2014 Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the Expression of XCR1 and SIRPα. Frontiers in immunology 48 25120540
2023 XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors. Proceedings of the National Academy of Sciences of the United States of America 46 37566635
2020 Cross-Presenting XCR1+ Dendritic Cells as Targets for Cancer Immunotherapy. Cells 44 32121071
2022 TIM-3 blockade enhances IL-12-dependent antitumor immunity by promoting CD8+ T cell and XCR1+ dendritic cell spatial co-localization. Journal for immunotherapy of cancer 43 34987021
2016 Microglial Inhibition Influences XCL1/XCR1 Expression and Causes Analgesic Effects in a Mouse Model of Diabetic Neuropathy. Anesthesiology 43 27387353
2016 Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells. Journal of immunological methods 41 26966045
1999 Mapping of the CCXCR1, CX3CR1, CCBP2 and CCR9 genes to the CCR cluster within the 3p21.3 region of the human genome. Cytogenetics and cell genetics 40 10702689
2010 Conservation of a chemokine system, XCR1 and its ligand, XCL1, between human and mice. Biochemical and biophysical research communications 39 20541533
2014 TLR3-responsive, XCR1+, CD141(BDCA-3)+/CD8α+-equivalent dendritic cells uncovered in healthy and simian immunodeficiency virus-infected rhesus macaques. Journal of immunology (Baltimore, Md. : 1950) 38 24740505
2021 PD-L1+ and XCR1+ dendritic cells are region-specific regulators of gut homeostasis. Nature communications 37 34389726
2015 Cross-presentation of cutaneous melanoma antigen by migratory XCR1+CD103- and XCR1+CD103+ dendritic cells. Oncoimmunology 35 26405572
2018 IL-27p28 Production by XCR1+ Dendritic Cells and Monocytes Effectively Predicts Adjuvant-Elicited CD8+ T Cell Responses. ImmunoHorizons 34 29354801
2017 Targeting Influenza Virus Hemagglutinin to Xcr1+ Dendritic Cells in the Absence of Receptor-Mediated Endocytosis Enhances Protective Antibody Responses. Journal of immunology (Baltimore, Md. : 1950) 33 28228559
2019 Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1+ Dendritic Cells. Cell reports 32 31577946
2010 Functional expression of the chemokine receptor XCR1 on oral epithelial cells. The Journal of pathology 30 20225245
2004 Up-regulation of XCR1 expression in rheumatoid joints. Rheumatology (Oxford, England) 30 14970401
2008 Immunomodulation by herpesvirus U51A chemokine receptor via CCL5 and FOG-2 down-regulation plus XCR1 and CCR7 mimicry in human leukocytes. European journal of immunology 28 18286574
2000 Identification of viral macrophage inflammatory protein (vMIP)-II as a ligand for GPR5/XCR1. Biochemical and biophysical research communications 27 10679309
2016 In Vitro Generation of Human XCR1(+) Dendritic Cells from CD34(+) Hematopoietic Progenitors. Methods in molecular biology (Clifton, N.J.) 26 27142006
2015 XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer. Biochemical and biophysical research communications 25 26166822
2018 Structure-Function Relationship of XCL1 Used for in vivo Targeting of Antigen Into XCR1+ Dendritic Cells. Frontiers in immunology 24 30619244
2016 Expanding the tools for identifying mononuclear phagocyte subsets in swine: Reagents to porcine CD11c and XCR1. Developmental and comparative immunology 24 27345169
2019 Structure-function guided modeling of chemokine-GPCR specificity for the chemokine XCL1 and its receptor XCR1. Science signaling 21 31481523
2021 Development of novel reagents to chicken FLT3, XCR1 and CSF2R for the identification and characterization of avian conventional dendritic cells. Immunology 20 34767637
2018 XCL1-XCR1 pathway promotes trophoblast invasion at maternal-fetal interface by inducing MMP-2/MMP-9 activity. American journal of reproductive immunology (New York, N.Y. : 1989) 20 29856101
2022 New insights into the analgesic properties of the XCL1/XCR1 and XCL1/ITGA9 axes modulation under neuropathic pain conditions - evidence from animal studies. Frontiers in immunology 19 36618360
2009 Spatially restricted translation of the xCR1 mRNA in Xenopus embryos. Molecular and cellular biology 19 19364820
2024 Inflammatory response in traumatic brain and spinal cord injury: The role of XCL1-XCR1 axis and T cells. CNS neuroscience & therapeutics 18 38887195
2022 The liver contains distinct interconnected networks of CX3CR1+ macrophages, XCR1+ type 1 and CD301a+ type 2 conventional dendritic cells embedded within portal tracts. Immunology and cell biology 18 35718354
2017 The role of the chemokine receptor XCR1 in breast cancer cells. Breast cancer (Dove Medical Press) 18 28408852
2018 Transcriptomic analyses of chemokines reveal that down-regulation of XCR1 is associated with advanced hepatocellular carcinoma. Biochemical and biophysical research communications 17 29408492
2018 A Novel Role for Lymphotactin (XCL1) Signaling in the Nervous System: XCL1 Acts via its Receptor XCR1 to Increase Trigeminal Neuronal Excitability. Neuroscience 17 29588250
2013 Cytomegalovirus expresses the chemokine homologue vXCL1 capable of attracting XCR1+ CD4- dendritic cells. Journal of virology 17 24155383
2023 XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections. Cell reports 16 36795562
2020 Traumatic brain injury in mice induces changes in the expression of the XCL1/XCR1 and XCL1/ITGA9 axes. Pharmacological reports : PR 15 33185818
2017 The anti-influenza M2e antibody response is promoted by XCR1 targeting in pig skin. Scientific reports 15 28794452
2011 XCR1 expression and biased VH gene usage are distinct features of diffuse large B-cell lymphoma initially manifesting in the bone marrow. American journal of clinical pathology 14 21411777
2025 The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity. The Journal of experimental medicine 12 39841133
2024 Molecular basis for chemokine recognition and activation of XCR1. Proceedings of the National Academy of Sciences of the United States of America 12 39565315
2023 XCR1+ conventional dendritic cell-induced CD4+ T helper 1 cell activation exacerbates cardiac remodeling after ischemic myocardial injury. Journal of molecular and cellular cardiology 12 36739942
2024 RUNX2 Phase Separation Mediates Long-Range Regulation Between Osteoporosis-Susceptibility Variant and XCR1 to Promote Osteoblast Differentiation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 11 39704037
2023 Development and function of chicken XCR1+ conventional dendritic cells. Frontiers in immunology 11 37954617
2019 CD8+XCR1neg Dendritic Cells Express High Levels of Toll-Like Receptor 5 and a Unique Complement of Endocytic Receptors. Frontiers in immunology 11 30700986
2019 Tolerogenic XCR1+ dendritic cell population is dysregulated in HLA-B27 transgenic rat model of spondyloarthritis. Arthritis research & therapy 10 30717755
2022 Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection. Frontiers in immunology 9 35296089
2022 Reduced T Cell Priming in Microbially Experienced "Dirty" Mice Results from Limited IL-27 Production by XCR1+ Dendritic Cells. Journal of immunology (Baltimore, Md. : 1950) 8 36426978
2019 Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes. Frontiers in immunology 8 31191552
2019 Rat cytomegalovirus-encoded γ-chemokine vXCL1 is a highly adapted, species-specific agonist for rat XCR1-positive dendritic cells. Journal of cell science 7 31649144
2017 Identification and expression analysis of three XCR1-like receptors from Epinephelus coioides after Cryptocaryon irritans infection. Fish & shellfish immunology 6 28587832
2004 cCXCR1 is a receptor for cIL-8 (9E3/cCAF) and its N- and C-terminal peptides and is also activated by hIL-8 (CXCL8). Journal of leukocyte biology 6 15576419
2019 Genetic diversity of chemokine XCL1 and its receptor XCR1 in murine rodents. Developmental and comparative immunology 5 31026469
2017 The Identification and Distribution of Cattle XCR1 and XCL1 among Peripheral Blood Cells: New Insights into the Design of Dendritic Cells Targeted Veterinary Vaccine. PloS one 5 28129380
2024 Infectious bronchitis virus vaccination, but not the presence of XCR1, is correlated with large differences in chicken caecal microbiota. Microbial genomics 4 39222347
2021 Selective involution of thymic medulla by cyclosporine A with a decrease of mature thymic epithelia, XCR1+ dendritic cells, and epithelium-free areas containing Foxp3+ thymic regulatory T cells. Histochemistry and cell biology 4 33993340
2025 The XCL1/XCR1 axis is upregulated in type 1 diabetes and aggravates its pathogenesis. JCI insight 3 40014407
2016 In Vivo Ablation of a Dendritic Cell Subset Expressing the Chemokine Receptor XCR1. Methods in molecular biology (Clifton, N.J.) 3 27142021
2025 Long Non-Coding RNA Osr2 Promotes Fusarium solani Keratitis Inflammation via the miR-30a-3p/ Xcr1 Axis. Investigative ophthalmology & visual science 2 40067293
2025 Xcr1+ type 1 conventional dendritic cells are essential mediators for atherosclerosis progression. eLife 2 40934103
2026 Targeting donor XCR1+ and CD11b+ dendritic cells prevents Th1- and Th17-dependent GVHD within the gastrointestinal tract. Blood 1 41662631
2025 Intratumoral delivery of FLT3L with CXCR3/CCR5 ligands promotes XCR1+ cDC1 infiltration and activates anti-tumor immunity. Nature communications 1 41469380
2023 Therapeutically targeting type I interferon directly to XCR1+ dendritic cells reveals the role of cDC1s in anti-drug antibodies. Frontiers in immunology 1 37942313
2026 Metabolic Reprogramming Driven by Trophoblasts and Decidual XCR1+PMN-MDSC Crosstalk Controls Adverse Outcomes Associated With Advanced Maternal Age. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41524173
2026 XCR1+ Conventional Type 1 Dendritic Cells Exacerbate the Inflammation in Osteogenic Arthritis Through IL-17A+CD8+ T Cells. Arthritis & rheumatology (Hoboken, N.J.) 0 41640334
2026 Shared autonomous HERV loci transcription identifies a unique circulating CD14+-xCR1+ mononuclear cell phenotype in a patient group with post-acute sequelae of COVID-19. PloS one 0 42154742
2017 [Cloning and in vitro expression of XCR1 of Rhesus macaque]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 28395709

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