title: CCL25 induces α₄β₇ integrin-dependent migration of IL-17⁺ γδ T lymphocytes during an allergic reaction.
abstract: Herein, we provide evidence that during allergic inflammation, CCL25 induces the selective migration of IL-17(+) γδ T cells mediated by α(4) β(7) integrin. Intrapleural injection of CCL25 into ovalbumin (OVA)-immunized C57BL/6 mice triggered the accumulation of γδ T lymphocytes expressing CCR9 (CCL25 receptor) and α(4) β(7) 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(+) , α(4) β(7) (+) , 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 α(4) β(7) 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/α(4) β(7) integrin pathway is selective for γδ T cells. In addition, α(4) β(7) integrin blockade impaired the in vitro transmigration of γδ T cells across endothelium (which expresses α(4) β(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(+) γδ T-cell mobilization to inflamed tissue via α(4) β(7) integrin and modulates IL-17 levels.
authors.affiliation: Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Maria F S
authors.initials: MF
authors.lastname: Costa
authors.forename: Victor U
authors.initials: VU
authors.lastname: Bornstein
authors.forename: André L
authors.initials: AL
authors.lastname: Candéa
authors.forename: Andréa
authors.initials: A
authors.lastname: Henriques-Pons
authors.forename: Maria G
authors.initials: MG
authors.lastname: Henriques
authors.forename: Carmen
authors.initials: C
authors.lastname: Penido
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology; D019742:Chemokines, CC / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D016023:Integrins / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins; D010998:Pleurisy / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D054388:Receptors, CCR / Q000276:immunology; D054399:Receptors, CCR6 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
chemical_list: C119309:CC chemokine receptor 9; C498126:CCR6 protein, mouse; C491541:Ccl25 protein, mouse; D015815:Cell Adhesion Molecules; D019742:Chemokines, CC; D016023:Integrins; D020381:Interleukin-17; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054388:Receptors, CCR; D054399:Receptors, CCR6; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7