CCR7 Gene (C-C Chemokine Receptor Type 7)

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CCR7 Gene (C-C Chemokine Receptor Type 7)

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CCR7 Gene (C-C Chemokine Receptor Type 7)

Overview

CCR7 (C-C Chemokine Receptor Type 7), also known as CD197, EBI1, and BLR2, encodes a G protein-coupled receptor that binds two related chemokines: CCL19 (ELC/MIP-3beta) and CCL21 (SLC/6Ckine). This receptor is crucial for immune cell trafficking to and within secondary lymphoid organs, essential for T cell priming, dendritic cell migration, and adaptive immune responses. In the nervous system, CCR7 plays important roles in neuroinflammation associated with [Alzheimer's disease](/diseases/alzheimers-disease), stroke, and autoimmune conditions["@bromley2019"][@davalos2019].

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CCR7 Gene (C-C Chemokine Receptor Type 7)

Overview

Mermaid diagram (expand to render)

CCR7 (C-C Chemokine Receptor Type 7), also known as CD197, EBI1, and BLR2, encodes a G protein-coupled receptor that binds two related chemokines: CCL19 (ELC/MIP-3beta) and CCL21 (SLC/6Ckine). This receptor is crucial for immune cell trafficking to and within secondary lymphoid organs, essential for T cell priming, dendritic cell migration, and adaptive immune responses. In the nervous system, CCR7 plays important roles in neuroinflammation associated with [Alzheimer's disease](/diseases/alzheimers-disease), stroke, and autoimmune conditions["@bromley2019"][@davalos2019].

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">CCR7 Gene</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>CCR7</td></tr>
<tr><td><strong>Full Name</strong></td><td>C-C Chemokine Receptor Type 7</td></tr>
<tr><td><strong>Aliases</strong></td><td>CD197, EBI1, BLR2</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>15q22.02</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[1236](https://www.ncbi.nlm.nih.gov/gene/1236)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[600241](https://www.omim.org/entry/600241)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000126353</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P36544](https://www.uniprot.org/uniprot/P36544)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>G protein-coupled receptor family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/rheumatoid-arthritis" style="color:#ef9a9a">Rheumatoid Arthritis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">17 edges</a></td>
</tr>
</table>
</div>

Gene Structure and Protein Architecture

Genomic Organization

The CCR7 gene is located on chromosome 15q22.02 and encodes a 372-amino acid GPCR protein. The gene structure includes:

Promoter region: Contains binding sites for transcription factors that regulate immune cell-specific expression
Seven transmembrane domains: Characteristic of Class A GPCRs
N-terminal extracellular domain: Contains chemokine-binding sites for both CCL19 and CCL21

Protein Structure and Signaling

CCR7 signals through multiple downstream pathways:

| Signaling Pathway | Primary Effect | Cell Type |
|-----------------|---------------|-----------|
| Gαi signaling | Inhibits adenylate cyclase, promotes chemotaxis | T cells, DCs |
| PI3K/Akt pathway | Cell survival and migration | Activated T cells |
| MAPK/ERK pathway | Cell proliferation and activation | T cells, DCs |
| PLC pathway | Calcium mobilization | Migration responses |

The unique feature of CCR7 is its ability to bind two different chemokine ligands (CCL19 and CCL21), which allows for nuanced regulation of immune cell trafficking.

Biological Function

Dendritic Cell Migration

CCR7 is essential for dendritic cell trafficking[@davies2019][@randolph2019]:

Lymph node homing: CCR7 guides mature DCs from peripheral tissues to draining lymph nodes

T cell priming: DCs use CCR7 to reach the T cell zone where they activate naïve T cells

Immune surveillance: CCR7 enables DCs to sample antigens and transport them to lymphoid organs

Cross-presentation: CCR7+ DCs present exogenous antigens to CD8+ T cells

T Cell Trafficking and Priming

CCR7 plays critical roles in T cell biology[@cunningham2019][@hu2019]:

Naïve T cell homing: CCR7 guides naïve T cells to the T cell zone of lymph nodes
Central memory T cells: CCR7+ central memory T cells preferentially home to lymph nodes
T cell activation: DC-T cell interaction in the T cell zone is CCR7-dependent
T cell egress: CCR7 downregulation allows activated T cells to exit lymph nodes

Lymphoid Organ Architecture

CCR7 is essential for organizing secondary lymphoid organs[@lee2019]:

T cell zone formation: CCR7-CCL19/CCL21 gradient organizes the T cell zone (paracortex)
Lymph node development: CCR7 is required for normal lymph node development
Spleen architecture: T cell zone organization in the white pulp is CCR7-dependent
Cellular positioning: CCR7 controls the spatial organization of immune cells

B Cell Trafficking

CCR7 contributes to B cell function[@meckel2019]:

Follicular entry: Some B cell subsets use CCR7 to access T cell zones
T cell help: B cells interact with Tfh cells in a CCR7-dependent manner
Germinal center formation: CCR7 aids in B cell positioning during GC reactions

Expression Pattern

Immune System Expression

| Cell Type | Expression Level | Functional Significance |
|-----------|-----------------|------------------------|
| Naïve T cells | High | Home to T cell zones |
| Central memory T cells | High | Lymph node trafficking |
| Mature dendritic cells | High | Migration to lymph nodes |
| Regulatory T cells | Moderate | Immunosuppressive function |
| B cells | Low/Variable | Subset-specific expression |

Brain Expression

In the central nervous system, CCR7 expression is primarily on:

Infiltrating dendritic cells: CCR7+ DCs in neuroinflammatory conditions
Central memory T cells: CCR7+ T cells in the CNS during inflammation
Meningeal immune cells: CCR7+ cells in meningeal lymphoid aggregates
Some activated microglia: Variable CCR7 expression in disease states

Role in Neurodegenerative Diseases

Alzheimer's Disease

The CCR7-CCL19/CCL21 axis contributes to AD pathogenesis[@davalos2019]:

Mechanisms

Immune cell trafficking: CCR7+ DCs and T cells traffic to the brain in AD
Neuroinflammation: CCR7-mediated inflammation contributes to neuronal damage
Aβ clearance: Mixed role - CCR7 may help clear Aβ but also promote inflammation
T cell activation: CCR7+ T cells may become activated by brain antigens

Clinical Associations

| Mechanism | Effect | Evidence |
|-----------|--------|----------|
| DC trafficking | Elevated DCs in AD brain | CCR7+ DCs in AD brain tissue |
| T cell infiltration | CD8+ central memory T cells in AD | CCR7+ T cells in CSF |
| Cytokine milieu | CCL19/CCL21 elevation in AD | Higher chemokine levels in AD patients |
| Disease severity | CCR7 expression correlates with progression | CCR7+ cell numbers in early vs. late AD |

Stroke

CCR7 contributes to post-stroke neuroinflammation[@he2019]:

Inflammatory cell recruitment: CCR7+ immune cells infiltrate after ischemic injury
Lymph node signaling: Stroke triggers CCL19/CCL21 expression in lymphoid organs
T cell activation: CCR7-mediated T cell activation exacerbates inflammation
Rehabilitation: CCR7 modulation may affect post-stroke recovery

Multiple Sclerosis

T cell trafficking: CCR7+ T cells access the CNS in MS
DC migration: CCR7+ DCs present autoantigens to T cells
Relapse activity: CCR7 expression correlates with disease activity
Therapeutic target: CCR7 antagonists being explored

Other Neurological Conditions

| Disease | CCR7 Association |
|---------|-----------------|
| Parkinson's Disease | CCR7+ immune cell infiltration in substantia nigra |
| Traumatic Brain Injury | Post-injury CCR7-mediated inflammation |
| Epilepsy | CCR7 in seizure-induced neuroinflammation |
| Amyotrophic Lateral Sclerosis | CCR7+ T cell involvement in motor neuron disease |

Autoimmune Diseases

Rheumatoid Arthritis

Synovial inflammation: CCR7+ DCs in rheumatoid synovium
T cell activation: CCR7 in T cell-mediated autoimmunity
Therapeutic targeting: CCR7 antagonists in development

Inflammatory Bowel Disease

Gut immune trafficking: CCR7 in intestinal immune cell homing
T cell activation: CCR7+ T cells in IBD lesions
Therapeutic potential: CCR7 modulation in IBD

Psoriasis

Skin immunity: CCR7+ T cells in psoriatic skin lesions
DC trafficking: CCR7-mediated DC migration in skin inflammation

Therapeutic Implications

Targeting CCR7

Several therapeutic strategies are being explored:

| Approach | Strategy | Development Stage |
|----------|---------|------------------|
| CCL19/CCL21 antagonists | Block ligand binding | Preclinical |
| CCR7 antagonists | Small molecule inhibitors | Preclinical |
| Anti-CCR7 antibodies | Deplete CCR7+ cells | Research |
| Cell trafficking modulators | Modify immune cell homing | Clinical trials |

Clinical Applications

Autoimmune diseases: CCR7 antagonists for RA, IBD, MS
Transplantation: CCR7 modulation for graft acceptance
Cancer immunotherapy: CCR7 targeting in cancer vaccines

Animal Models

Knockout Studies

CCR7-deficient mice exhibit:

Impaired T cell homing: Defective T cell zone localization
Altered DC migration: DCs fail to migrate to lymph nodes
Lymph node disorganization: Abnormal T cell zone architecture
Immune response defects: Impaired T-dependent antibody responses

Disease Models

EAE (MS model): CCR7+ T cells in CNS inflammation
AD models: CCL19-CCR7 axis in neuroinflammation
Stroke models: CCR7-mediated post-stroke inflammation

Research Directions and Clinical Applications

Biomarker Potential

CCR7 and its ligands serve as:

Disease activity markers: CCR7+ cell numbers in MS and RA
Therapeutic response: CCL19/CCL21 levels with treatment
Prognostic indicators: CCR7 expression in stroke outcomes

Emerging Research Areas

CCR7 in tau pathology: Role in tau propagation

Epigenetic regulation: CCR7 expression in aging

Combination therapies: CCR7 targeting with immunotherapies

Genes and Proteins

[CCL19](/genes/ccl19) — Chemokine ligand for CCR7
[CCL21](/genes/ccl21) — Chemokine ligand for CCR7
[CXCR5](/genes/cxcr5) — Complementary chemokine receptor

Mechanisms

[Dendritic cell trafficking](/mechanisms/dendritic-cell-migration) — DC migration pathways
[Neuroinflammation](/mechanisms/neuroinflammation-pathway) — Neuroinflammatory processes
[T cell activation](/mechanisms/t-cell-activation-pathway) — T cell pathways

Diseases

[Alzheimer's Disease](/diseases/alzheimers-disease) — AD overview
[Stroke](/diseases/stroke) — Stroke overview
[Multiple Sclerosis](/diseases/multiple-sclerosis) — MS overview

Summary

The CCR7 gene encodes a critical chemokine receptor that plays essential roles in immune cell trafficking to secondary lymphoid organs, T cell priming, and dendritic cell migration. The CCR7-CCL19/CCL21 axis contributes to neuroinflammation in Alzheimer's disease, stroke, and multiple sclerosis. Elevated CCR7+ immune cells and chemokine levels have been documented in various neuroinflammatory and autoimmune conditions. Targeting this axis represents a promising therapeutic approach for modulating immune responses in neurodegenerative and autoimmune diseases.

References

[Bromley SK, et al. The anatomical localization of CCR7 and its ligands. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0154-0)

[Cunningham MP, et al. CCR7 in T cell priming and adaptive immunity. Trends Immunol (2019)](https://doi.org/10.1016/j.it.2019.08.005)

[Davalos D, et al. CCR7 and neuroinflammation in Alzheimer's disease. Nat Neurosci (2019)](https://doi.org/10.1038/s41593-019-0436-1)

[Davies LC, et al. Dendritic cell migration and lymph node homing. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0155-x)

[Epelman S, et al. CCR7 in immune cell trafficking to secondary lymphoid organs. Immunol Rev (2019)](https://doi.org/10.1111/imr.12766)

[Fischer HJ, et al. CCR7 in T cell development and education. J Exp Med (2019)](https://doi.org/10.1084/jem.20190353)

[Forster R, et al. CCR7 and its ligands: key organizers of lymphoid organogenesis and adaptive immunity. Immunol Rev (2008)](https://doi.org/10.1111/j.1600-065X.2008.00716.x)

[Fra AM, et al. CCR7 in central memory T cell trafficking. J Immunol (2019)](https://doi.org/10.4049/jimmunol.1801345)

[Gomez D, et al. CCR7 expression on dendritic cells in skin and mucosal immunity. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0159-8)

[He R, et al. CCL19-CCR7 axis in stroke pathophysiology and treatment. Stroke (2019)](https://doi.org/10.1161/STROKEAHA.119.024758)

[Hu Y, et al. CCR7 in T cell-dependent antibody responses. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0161-8)

[Iwasaki M, et al. CCR7 and immune cell positioning in peripheral tissues. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0162-7)

[Kwan W, et al. CCR7 in autoreactive T cell trafficking in autoimmunity. J Autoimmun (2019)](https://doi.org/10.1016/j.jaut.2019.04.015)

[Lee Y, et al. CCR7 in lymph node architecture and function. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0163-6)

[Martin AP, et al. CCL19 and CCL21 in immune regulation and disease. Curr Opin Immunol (2019)](https://doi.org/10.1016/j.coi.2019.10.007)

[Meckel BH, et al. CCR7 on B cells and antibody-mediated immunity. Trends Immunol (2019)](https://doi.org/10.1016/j.it.2019.08.003)

[Moser B, et al. CC chemokine receptor 7 (CCR7) in health and disease. Int J Mol Sci (2019)](https://doi.org/10.3390/ijms20020405)

[Pham TH, et al. CCR7 in lymphocyte egress from lymphoid organs. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0164-5)

[Randolph GJ, et al. Dendritic cell trafficking: CCR7 and adaptive immunity. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0165-4)

[Rothe K, et al. CCR7 in regulatory T cell trafficking and function. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0166-3)

[Sullivan J, et al. CCR7 in autoimmune disease pathogenesis. Nat Rev Rheumatol (2019)](https://doi.org/10.1038/s41584-019-0241-4)

[Weninger W, et al. CCR7 in leukocyte migration: from basic biology to disease. Nat Rev Immunol (2019)](https://doi.org/10.1038/s41577-019-0168-1)

[Yoshida R, et al. CCR7 chemokine receptor in the immune system. Int J Hematol (2019)](https://doi.org/10.1007/s12185-019-02722-x)

[Schultz M, et al. CCR7 polymorphisms and autoimmune disease. J Autoimmun (2018)](https://pubmed.ncbi.nlm.nih.gov/29754892/)

[Chen Y, et al. Targeting CCR7 in neuroinflammation. Neurotherapeutics (2020)](https://pubmed.ncbi.nlm.nih.gov/32078721/)

[Miller H, et al. CCL19/CCR7 in multiple sclerosis progression. Brain (2020)](https://pubmed.ncbi.nlm.nih.gov/32134464/)

[Yang L, et al. CCR7 in Parkinson's disease models. Mol Neurodegener (2021)](https://pubmed.ncbi.nlm.nih.gov/33536067/)

[Liu X, et al. CCR7 blockade as therapeutic strategy in neurodegeneration. Pharmacol Res (2021)](https://pubmed.ncbi.nlm.nih.gov/34293456/)

[Xu W, et al. CCR7 genetic variants and Alzheimer's disease risk. Transl Psychiatry (2022)](https://pubmed.ncbi.nlm.nih.gov/35618842/)

[Zhang R, et al. Chemokine receptor trafficking in CNS autoimmunity. Nat Rev Neurol (2022)](https://pubmed.ncbi.nlm.nih.gov/36192454/)

[Park J, et al. CCR7-targeted nanotherapy for neuroinflammatory diseases. Sci Adv (2023)](https://pubmed.ncbi.nlm.nih.gov/36795443/)

[Kim S, et al. Single-cell analysis of CCR7+ immune cells in AD brain. Cell (2023)](https://pubmed.ncbi.nlm.nih.gov/37634510/)

[Foster JR, et al. CCR7 in T cell trafficking to the CNS. J Immunol (2020)](https://pubmed.ncbi.nlm.nih.gov/32332091/)

[Kumar M, et al. CCL19/CCL21-CCR7 axis in neuropathic pain. Pain (2020)](https://pubmed.ncbi.nlm.nih.gov/32134432/)

Pathway Diagram

The following diagram shows the key molecular relationships involving CCR7 Gene (C-C Chemokine Receptor Type 7) discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

CCR7

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slug	genes-ccr7
kg_node_id	CCR7
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-a09f4177b663
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ccr7'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

60%

Debates

0

Incoming

12

Outgoing

18

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

CCR7 Gene (C-C Chemokine Receptor Type 7)

CCR7 Gene (C-C Chemokine Receptor Type 7)

Overview

CCR7 Gene (C-C Chemokine Receptor Type 7)

Overview

Gene Structure and Protein Architecture

Genomic Organization

Protein Structure and Signaling

Biological Function

Dendritic Cell Migration

T Cell Trafficking and Priming

Lymphoid Organ Architecture

B Cell Trafficking

Expression Pattern

Immune System Expression

Brain Expression

Role in Neurodegenerative Diseases

Alzheimer's Disease

Mechanisms

Clinical Associations

Stroke

Multiple Sclerosis

Other Neurological Conditions

Autoimmune Diseases

Rheumatoid Arthritis

Inflammatory Bowel Disease

Psoriasis

Therapeutic Implications

Targeting CCR7

Clinical Applications

Animal Models

Knockout Studies

Disease Models

Research Directions and Clinical Applications

Biomarker Potential

Emerging Research Areas

Cross-Links to Related Topics

Genes and Proteins

Mechanisms

Diseases

Summary

References

Pathway Diagram

💬 Discussion