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

Authors

  • Maria F. S. Costa,

    1. Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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  • Victor U. Bornstein,

    1. Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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  • André L. Candéa,

    1. Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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  • Andréa Henriques-Pons,

    1. Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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  • Maria G. Henriques,

    1. Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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    • These authors contributed equally to this work.

  • and Carmen Penido

    Corresponding author
    1. Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
    • Full correspondence: Dr. Carmen Penido, Laboratório de Farmacologia Aplicada, Departamento de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ, CEP 21041-250, Brazil

      Fax: +55-21 39772422

      e-mail: cpenido@far.fiocruz.brSee accompanying Commentary:http://dx.doi.org/10.1002/eji.201142545

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    • These authors contributed equally to this work.


  • See accompanying Commentary by Silva Santos

Abstract

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.

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