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-3β) 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, stroke, and autoimmune conditions[1][2].
| CCR7 Gene | |
|---|---|
| Gene Symbol | CCR7 |
| Full Name | C-C Chemokine Receptor Type 7 |
| Aliases | CD197, EBI1, BLR2 |
| Chromosomal Location | 15q22.02 |
| NCBI Gene ID | [1236](https://www.ncbi.nlm.nih.gov/gene/1236) |
| OMIM | [600241](https://www.omim.org/entry/600241) |
| Ensembl ID | ENSG00000126353 |
| UniProt ID | [P36544](https://www.uniprot.org/uniprot/P36544) |
| Protein Family | G protein-coupled receptor family |
The CCR7 gene is located on chromosome 15q22.02 and encodes a 372-amino acid GPCR protein. The gene structure includes:
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.
CCR7 is essential for dendritic cell trafficking[3][4]:
CCR7 plays critical roles in T cell biology[5][6]:
CCR7 is essential for organizing secondary lymphoid organs[7]:
CCR7 contributes to B cell function[8]:
| 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 |
In the central nervous system, CCR7 expression is primarily on:
The CCR7-CCL19/CCL21 axis contributes to AD pathogenesis[2:1]:
| 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 |
CCR7 contributes to post-stroke neuroinflammation[9]:
| 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 |
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 |
CCR7-deficient mice exhibit:
CCR7 and its ligands serve as:
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.
Bromley SK, et al. The anatomical localization of CCR7 and its ligands. Nat Rev Immunol. 2019. ↩︎
Davalos D, et al. CCR7 and neuroinflammation in Alzheimer's disease. Nat Neurosci. 2019. ↩︎ ↩︎
Davies LC, et al. Dendritic cell migration and lymph node homing. Nat Rev Immunol. 2019. ↩︎
Randolph GJ, et al. Dendritic cell trafficking: CCR7 and adaptive immunity. Nat Rev Immunol. 2019. ↩︎
Cunningham MP, et al. CCR7 in T cell priming and adaptive immunity. Trends Immunol. 2019. ↩︎
Hu Y, et al. CCR7 in T cell-dependent antibody responses. Nat Rev Immunol. 2019. ↩︎
Lee Y, et al. CCR7 in lymph node architecture and function. Nat Rev Immunol. 2019. ↩︎
Meckel BH, et al. CCR7 on B cells and antibody-mediated immunity. Trends Immunol. 2019. ↩︎
He R, et al. CCL19-CCR7 axis in stroke pathophysiology and treatment. Stroke. 2019. ↩︎