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Ccr9  -  chemokine (C-C motif) receptor 9

Mus musculus

Synonyms: A130091K22Rik, C-C CKR-9, C-C chemokine receptor type 9, CC-CKR-9, CCR-9, ...
 
 
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Disease relevance of Ccr9

 

High impact information on Ccr9

  • These recently activated CCR9(+) CD8alphabeta(+) lymphocytes selectively localized to the small-intestinal mucosa, and in vivo neutralization of the CCR9 ligand, CCL25, reduced the ability of these cells to populate the small-intestinal epithelium [2].
  • Using a T cell receptor transgenic transfer model, we demonstrate that CCR9 expression is functionally maintained on CD8alphabeta(+) lymphocytes following activation in mesenteric lymph nodes but rapidly downregulated on CD8alphabeta(+) lymphocytes activated in peripheral lymph nodes [2].
  • Here we show that the CC chemokine receptor 9 (CCR9) is selectively and functionally expressed on murine alpha(E)beta(7)(+) naive CD8alphabeta(+) lymphocytes and a subset of recently activated CD69(+) CD8alphabeta(+) lymphocytes [2].
  • Together these results demonstrate an important role for chemokines in the localization of T lymphocytes to the small-intestinal mucosa and suggest that targeting CCL25 and/or CCR9 may provide a means to selectively modulate small-intestinal immune responses [2].
  • Background & Aims: CCL25 mediates the homeostatic recruitment of CCR9-expressing lymphocytes to the small intestine, but the function of this chemokine/receptor pair during chronic small intestinal inflammation has yet to be determined [1].
 

Biological context of Ccr9

 

Anatomical context of Ccr9

  • In spite of the high level of CCR9 found in double- and single-positive thymocytes and of the expression of its corresponding ligand on thymic stromal cells, CCR9 deletion had no major effect on intrathymic T-cell development [3].
  • Finally, it was shown that in the small intestine of CCR9-deficient mice, the intraepithelial T-cell-to-epithelial cell ratio is decreased, an observation that can be accounted for by a marked diminution of the T-cell receptor gammadelta(+) compartment [3].
  • Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes [3].
  • GPR-9-6 mRNA is present at high levels in the thymus, and by RT-PCR analysis its expression is induced as normal thymocytes undergo the double negative to double positive transition [5].
  • CCR9 was also found in the mossy fibres and/or terminals, suggesting an axonal or presynaptic localization, and CCR10 in apical dendrites of pyramidal neurons in the CA1 area [6].
 

Associations of Ccr9 with chemical compounds

  • Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9) [7].
 

Other interactions of Ccr9

  • By using anti-CD3varepsilon treatment of recombinase-activating gene 2 (Rag2-/-) mice to mimic pre-TCR signaling and drive thymocyte development to the double positive stage, we have identified murine GPR-9-6 as a chemokine receptor whose expression is strongly induced following pre-TCR signaling [5].
  • However, competitive transplantation experiments revealed that bone marrow from CCR9(-/-) mice was less efficient at repopulating the thymus of lethally irradiated Rag-1(-/-) mice than bone marrow from littermate CCR9(+/+) mice [8].

References

  1. Antibody Blockade of CCL25/CCR9 Ameliorates Early but not Late Chronic Murine Ileitis. Rivera-Nieves, J., Ho, J., Bamias, G., Ivashkina, N., Ley, K., Oppermann, M., Cominelli, F. Gastroenterology (2006) [Pubmed]
  2. CCL25 mediates the localization of recently activated CD8alphabeta(+) lymphocytes to the small-intestinal mucosa. Svensson, M., Marsal, J., Ericsson, A., Carramolino, L., Brodén, T., Márquez, G., Agace, W.W. J. Clin. Invest. (2002) [Pubmed]
  3. Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes. Wurbel, M.A., Malissen, M., Guy-Grand, D., Meffre, E., Nussenzweig, M.C., Richelme, M., Carrier, A., Malissen, B. Blood (2001) [Pubmed]
  4. Characterization of CCR9 expression and CCL25/thymus-expressed chemokine responsiveness during T cell development: CD3(high)CD69+ thymocytes and gammadeltaTCR+ thymocytes preferentially respond to CCL25. Uehara, S., Song, K., Farber, J.M., Love, P.E. J. Immunol. (2002) [Pubmed]
  5. Murine CCR9, a chemokine receptor for thymus-expressed chemokine that is up-regulated following pre-TCR signaling. Norment, A.M., Bogatzki, L.Y., Gantner, B.N., Bevan, M.J. J. Immunol. (2000) [Pubmed]
  6. CCR7, CCR8, CCR9 and CCR10 in the mouse hippocampal CA1 area and the dentate gyrus during and after pilocarpine-induced status epilepticus. Liu, J.X., Cao, X., Tang, Y.C., Liu, Y., Tang, F.R. J. Neurochem. (2007) [Pubmed]
  7. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Mora, J.R., Bono, M.R., Manjunath, N., Weninger, W., Cavanagh, L.L., Rosemblatt, M., Von Andrian, U.H. Nature (2003) [Pubmed]
  8. A role for CCR9 in T lymphocyte development and migration. Uehara, S., Grinberg, A., Farber, J.M., Love, P.E. J. Immunol. (2002) [Pubmed]
 
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