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Publication : CCL25 induces α₄β₇ integrin-dependent migration of IL-17⁺ γδ T lymphocytes during an allergic reaction.

First Author  Costa MF Year  2012
Journal  Eur J Immunol Volume  42
Issue  5 Pages  1250-60
PubMed ID  22539297 Mgi Jnum  J:187772
Mgi Id  MGI:5438174 Doi  10.1002/eji.201142021
Citation  Costa MF, et al. (2012) CCL25 induces alpha(4)beta(7) integrin-dependent migration of IL-17(+) gammadelta T lymphocytes during an allergic reaction. Eur J Immunol 42(5):1250-60
abstractText  Herein, we provide evidence that during allergic inflammation, CCL25 induces the selective migration of IL-17(+) gammadelta T cells mediated by alpha(4) beta(7) integrin. Intrapleural injection of CCL25 into ovalbumin (OVA)-immunized C57BL/6 mice triggered the accumulation of gammadelta T lymphocytes expressing CCR9 (CCL25 receptor) and alpha(4) beta(7) integrin in the pleura, but failed to attract alphabeta T lymphocytes. CCL25 attracted CCR6(+) gammadelta T cells producing IL-17 (but not IFN-gamma or IL-4). OVA challenge triggered increased production of CCL25 followed by the accumulation of CCR9(+) , alpha(4) beta(7) (+) , and CCR6(+) /IL-17(+) gammadelta T cells into the pleural cavities of OVA-immunized mice, which was inhibited by the in vivo neutralization of CCL25. The in vivo blockade of alpha(4) beta(7) integrin also inhibited the migration of IL-17(+) gammadelta T lymphocytes (but not of alphabeta T lymphocytes) into mouse pleura after OVA challenge, suggesting that the CCL25/alpha(4) beta(7) integrin pathway is selective for gammadelta T cells. In addition, alpha(4) beta(7) integrin blockade impaired the in vitro transmigration of gammadelta T cells across endothelium (which expresses alpha(4) beta(7) ligands VCAM-1 and MadCAM-1), which was induced by CCL25 and by cell-free pleural washes recovered from OVA-challenged mice. Our results reveal that during an allergic reaction, CCL25 drives IL-17(+) gammadelta T-cell mobilization to inflamed tissue via alpha(4) beta(7) integrin and modulates IL-17 levels.
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