Disease relevance of CCR9

• We characterize the role of TECK and CCR9-expresing lymphocytes in small intestinal Crohn's disease [1].
• Interleukin (IL)-2 and IL-4, together, down-regulated the expression and functions of CCR9 in T-ALL CD4+ T cells including chemotaxis and adhesion [2].
• The TECK-induced chemotaxis was sensitive to pertussis toxin and partially inhibited by Abs to CCR9 [3].
• Apj and CCR9 share with other coreceptors for HIV-1 and SIV an N-terminal region rich in aromatic and acidic residues [4].
• CONCLUSIONS: These studies suggest that the expression and activation of CCR9 affect cancer cell migration, invasion, and MMP expression, which together may affect prostate cancer metastasis [5].

High impact information on CCR9

• CCR9, CCL25 and alpha(4)beta(7) integrin were required for gut entry of CD8(+) RTEs [6].
• These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract [7].
• Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9(-) [7].
• GPR-9-6 is expressed on a subset of memory alpha4beta7(high) intestinal trafficking CD4 and CD8 lymphocytes [8].
• In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6 [8].

Biological context of CCR9

• Thymus-expressed chemokine, a ligand for CCR9, selectively induced T-ALL CD4+ T-cell chemotaxis and adhesion [2].
• We studied the phenotype and functional characteristics of CCR9(+) lymphocytes in blood from normal donors [9].
• Together, these results suggest that regulated expression of CCR9 is critical for normal development of immature thymocytes, but that down-regulation of CCR9 is not a prerequisite for thymocyte emigration [10].
• Furthermore, CD18(-/-) DO11.10 CD4(+) T cells primed in the intestinal secondary lymphoid organs demonstrate defects in up-regulation of the intestinal-specific trafficking molecules, alpha(4)beta(7) and CCR9 [11].
• Expression and functional role of CCR9 in prostate cancer cell migration and invasion [5].

Anatomical context of CCR9

• RESULTS: The fraction of CCR9(+) T cells in inflamed SB was significantly lower than in uninvolved SB mucosa [1].
• METHODS: CCR9 expression on lymphocytes from lamina propria, mesenteric lymph node, and peripheral blood was analyzed by flow cytometry and by Northern blotting for LPL [1].
• Our data suggest that TECK/CCR9 interaction may play a pivotal role in T-cell migration in the thymus [12].
• Among a panel of chemokines tested, TECK specifically induced calcium flux in CCR9-expressing cell lines [12].
• CCR9 and CXCR6 have not been described previously on primary NK cells [13].

Associations of CCR9 with chemical compounds

• Administration of CCR9 and/or Irg1 small interfering RNA alters the frequency and functional profiles of neurotoxic CCR9(+)Irg1(+) and neurosupportive CXCR3(+)Irg1(-) microglia in vivo [14].
• Induction of Tax by Cd(2+) in JPX-9, a subline of Jurkat human T cell line carrying Tax under the control of metallothionein promoter, led to upregulation of CCR9 [15].
• Gut dendritic cells and retinoic acid induce the expression of alpha4beta7 and CCR9 on T cells for their homing to the gut [16].
• We recently showed that activation of the CC chemokine 9 receptor (CCR9), a thymus-specific chemokine receptor, led to potent cFLIP(L)-independent resistance to cycloheximide-induced apoptosis and modest resistance to Fas-mediated apoptosis possibly via activation of multiple signaling components involving Akt and glycogen synthase kinase 3beta [17].

Other interactions of CCR9

• The transcription map also includes the CC chemokine receptor 9 gene (CCR9) and the LIM domain containing gene 1 (LIMD1) [18].
• Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes [8].
• We isolated cDNAs for a chemokine receptor-related protein having the database designation GPR-9-6 [19].
• Furthermore, a greater percentage of the breast milk CD8(+) T cells expressed the intestinal homing receptor, CD103, and the mucosal homing receptor CCR9 [20].

Analytical, diagnostic and therapeutic context of CCR9

• This notion was supported by the small number of CCR9+ naive T cells which was present shortly after thymectomy [21].
• Immunohistochemistry revealed that the leukemic cells in the gut still expressed CCR9 and colocalized with a high expression of the CCR9 ligand, CCL25 [22].
• RESULTS: The expression of cutaneous leukocyte antigen (CLA) and CC-chemokine receptor 4 (CCR4; associated with skin-homing) as well as the expression of integrin alpha4beta7 and CCR9 (associated with gut-homing) was analyzed on CD4+ memory T cells in CSF from individuals with non-inflammatory neurological diseases using flow cytometry [23].
• Thus, dissection of signaling components involved in the CCR9-mediated antiapoptosis could be a framework for cell survival mechanisms and may provide options for therapeutic interventions for neurdegenerative diseases or T cell malfunctioning [17].
• The study of beta-thalassemia was made by PCR-ARMS, the alpha genes by Southern blot, the phenotype of Hb Lepore by enzymatic amplification and the presence of -158 gamma G C-->T mutation by PCR and digestion with the restriction enzyme XmnL [24].

References