CCL25 induces α4β7 integrin‐dependent migration of IL‐17+γδ T lymphocytes during an allergic reaction

• Published in: European journal of immunology 2012-05, Vol.42 (5), p.1250-1260
• Main Authors: Costa, Maria F. S., Bornstein, Victor U., Candéa, André L., Henriques‐Pons, Andréa, Henriques, Maria G., Penido, Carmen
• Format: Article
• Language: English
• Subjects: Adhesion molecules; Allergy; Animals; CCL25; Cell Adhesion Molecules - immunology; Chemokines; Chemokines, CC - immunology; Chemotaxis, Leukocyte - immunology; Hypersensitivity - immunology; Integrins - immunology; Interleukin-17 - immunology; Mice; Mice, Inbred C57BL; Pleurisy - immunology; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, CCR - immunology; Receptors, CCR6 - immunology; T cells; T-Lymphocytes - immunology; Vascular Cell Adhesion Molecule-1 - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201142021

Herein, we provide evidence that during allergic inflammation, CCL25 induces the selec‐tive migration of IL‐17+ γδ T cells mediated by α4β7 integrin. Intrapleural injection of CCL25 into ovalbumin (OVA)‐immunized C57BL/6 mice triggered the accumulation of γδ T lymphocytes expressing CCR9 (CCL25 receptor) and α4β7 integrin in the pleura, but failed to attract αβ T lymphocytes. CCL25 attracted CCR6+ γδ T cells producing IL‐17 (but not IFN‐γ or IL‐4). OVA challenge triggered increased production of CCL25 followed by the accumulation of CCR9+, α4β7+, and CCR6+/IL‐17+ γδ 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 α4β7 integrin also inhibited the migration of IL‐17+ γδ T lymphocytes (but not of αβ T lymphocytes) into mouse pleura after OVA challenge, suggesting that the CCL25/α4β7 integrin pathway is selective for γδ T cells. In addition, α4β7 integrin blockade impaired the in vitro transmigration of γδ T cells across endothelium (which expresses α4β7 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+ γδ T‐cell mobilization to inflamed tissue via α4β7 integrin and modulates IL‐17 levels.