Disease relevance of CCR7

• Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases [1].
• We investigated the expression of CCL21 and CCR7 in chronic hepatitis C [2].
• Expression of CCR7 was also increased in patients with primary biliary cirrhosis [2].
• Thus, the CCL21/CCR7 signaling of fibrocytes may provide therapeutic targets for combating renal fibrosis [3].
• It has been reported recently that CD30 up-regulates the transcription of CCR7 mRNA in YT lymphoma cells [4].

Psychiatry related information on CCR7

• The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells [5].

High impact information on CCR7

• In mice lacking lymphoid CCL19 and CCL21 chemokines, or with B cells that lack CCR7, antigen engagement fails to cause movement to the T zone [6].
• We investigated this issue by analysing the expression of the chemokine receptor CCR7, which defines distinct subsets of naive and memory T lymphocytes with different homing and effector capacities and antiviral immune responses to HIV and cytomegalovirus [7].
• Another CC chemokine CCL21, which shares CCR7 with CCL19 but has a unique C-terminal extension containing positively charged amino acids, failed to show involvement in thymic emigration [8].
• Neonatal appearance of circulating T cells was defective in CCL19-neutralized mice as well as in CCR7-deficient mice but not in CCL21-neutralized mice [8].
• Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus [8].

Chemical compound and disease context of CCR7

• The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes [9].
• Stimulation with CCR7 ligands CCL19 and CCL21 inhibits apoptotic hallmarks of serum-deprived DCs, including membrane phosphatidylserine exposure, loss of mitochondria membrane potential, increased membrane blebs, and nuclear changes [10].
• Treatment with TSA or 5-Aza increased gene expression of both CCR7 and CXCR4 in melanoma lines [11].
• Because of the prominent role of the chemokine receptors CCR7 and CXCR5 in lymphocyte homing to secondary lymphoid organs, we hypothesized that they may also be involved in the action of FTY720, a synthetic immunosuppressant inducing lymphopenia [12].
• We show that transcription of the BLR2 gene could be specifically induced in Epstein-Barr virus negative BL 41 cells via estrogen-mediated activation of Epstein-Barr virus nuclear antigen 2, a key regulator of viral and cellular genes in immortalized B cells [13].

Biological context of CCR7

• Despite increased efficiency of uptake, interaction between iC3b-opsonized apoptotic cells and iDCs down-regulated the expression of major histocompatibility complex class II, CD86, CC chemokine receptor (CCR)2, CCR5, and beta2-integrins (P < 0.001), and up-regulated expression of CCR7 (P < 0.001) [14].
• Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model [2].
• The receptor for CCL21, CCR7, was also found to be highly expressed on the infiltrating T cells, most of which expressed the memory CD45Ro phenotype [15].
• Finally, CCR7 up-regulation in DCs exposed to LPS as well as migration toward CCL19/MIP-3beta were strongly impaired [16].
• Concomitantly, the expression of CCR7 and the migration to its ligand EBI1 ligand chemokine (ELC)/macrophage inflammatory protein (MIP)-3beta, a chemokine expressed in lymphoid organs, were strongly up-regulated, though with slower kinetics (24-48 h) [17].

Anatomical context of CCR7

• Immunohistochemical analysis on 13 LCH biopsies of bone, skin, and lymph node all expressed the immature dendritic cell (DC) marker CCR6 on the lesional LCs and absence of the mature DC marker CCR7 [18].
• We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest [19].
• CCR7 on T cells was analyzed by flow cytometry [2].
• Expression of CCR6 by pathologic LCs may contribute to their accumulation in nonlymphoid organs such as skin and bone, whereas CCR7 expression may direct them to lymphoid tissue [20].
• Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis [20].

Associations of CCR7 with chemical compounds

• Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells [21].
• A population with homing potential for lymph nodes (L selectin(+) CCR7(+)) exists only within a small subset of CD4 NKT cells [22].
• We summarize recent data on the function of CXCR5 and CCR7 and their intricate connection to the TNF/LT system in order to refine the current model of lymphoid organ development [23].
• Lipopolysaccharide stimulation of normal lymphocytes increased CXCR4 expression but decreased CCR5 and did not change CCR7 expression [24].
• AMD3100 did not, on its own, induce a calcium flux in the CCRF-CEM cells, which express multiple GPCRs including CXCR4, CCR4 and CCR7 [25].

Physical interactions of CCR7

• The BLR-1 protein has all the characteristics of a blue-light photoreceptor, whereas the structure of the deduced BLR-2 protein suggests that it interacts with BLR-1 through PAS domains to form a complex [26].
• Induction of G protein-coupled peptide receptor EBI 1 by human herpesvirus 6 and 7 infection in CD4+ T cells [27].

Regulatory relationships of CCR7

• CONCLUSIONS: Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs [2].
• SLC and ELC were also shown to fully share receptors expressed on cultured normal T cells known to express CCR7 [28].
• The strong allergen dinitrochlorobenzene slightly increased CCR7 expression on DCs but down-regulated CCR1 surface expression [29].
• CCR7 transcripts were minimally expressed in ex vivo and proliferating WC1(+)gammadelta T cells and CXCR5 expression was negligible [30].
• IL-4 promotes expression of CCR7, a marker linked to existing models of CD8(+) T cell differentiation [31].
• EP2 and EP4 agonists stimulated CCR7 in MCF-7 cells, whereas antagonists or small hairpin RNA of EP2 and EP4 attenuated CCR7 in MDA-MB-231 cells [32].

Other interactions of CCR7

• CD45RA(+)FOXP3(+) T cells mainly express lymphoid tissue homing receptors (CD62L, CCR7, and CXCR4), while CD45RO(+)FOXP3(+) T cells highly express both Th1 and Th2-associated trafficking receptors along with the lymphoid tissue homing receptors at reduced frequencies [33].
• By stably expressing five CC chemokine receptors (CCR1 to 5) and five orphan receptors, ELC-SEAP was found to bind specifically to an orphan receptor EBI1 [34].
• Within these samples, tumor mycosis fungoides cells exhibited high levels of CCR7, a chemokine receptor central for the entry of T cells to lymphatic tissue [35].
• CXCR4 expression on lymphocytes from septic patients was increased whereas CCR5 was decreased and CCR7 was unchanged [24].
• The mean fluorescent intensity (MFI) of the chemokine receptor expression on B-CLL cells was compared with normal controls and was not significantly different, except for an increase in the median expression of CXCR3 (P = .003) and CCR7 (P = .001) on B-CLL cells [36].

Analytical, diagnostic and therapeutic context of CCR7

• Reverse transcriptase-polymerase chain reaction and flow cytometric analysis, using anti-CCR7 monoclonal antibody (CCR7.6B3), revealed that ATL cells from patients with lymphoid organ involvement expressed significantly more CCR7/EBI1 than control CD4(+)CD45RO(+) T cells and ATL cells from patients without lymphoid organ involvement [37].
• EXPERIMENTAL DESIGN: Quantitative real-time reverse transcriptase-PCR (qRT) assay and immunohistochemistry (IHC) were used to assess the level of CCR7 expression in melanoma cell lines and in primary and metastatic melanoma tumors [38].
• By in situ hybridization, ELC and CCR7 mRNA were detected in the parafollicular and inner cortical regions of a lymph node, and in the parafollicular regions of an appendix [39].
• Following maturation induced by cluster designation (CD)40 ligation, the receptors for inflammatory chemokines are downregulated and CCR7 on P-DCs becomes coupled to migration [40].
• The disease-free survival and overall survival (OS) rates of patients exhibiting both CXCR4 and CCR7 expression were significantly reduced (P < 0.0001) [41].

References