CCL25 induces α 4β 7 integrin-dependent migration of IL-17 +γδ T lymphocytes during an allergic reaction

Maria F.S. Costa, Victor U. Bornstein, André L. Candéa, Andréa Henriques-Pons, Maria G. Henriques, Carmen Penido

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Herein, we provide evidence that during allergic inflammation, CCL25 induces the selec-tive migration of IL-17 + γδ T cells mediated by α 4β 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 4β 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 4β 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 4β 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 4β 7 integrin pathway is selective for γδ T cells. In addition, α 4β 7 integrin blockade impaired the in vitro transmigration of γδ T cells across endothelium (which expresses α 4β 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 4β 7 integrin and modulates IL-17 levels.

Original languageEnglish
Pages (from-to)1250-1260
Number of pages11
JournalEuropean Journal of Immunology
Issue number5
StatePublished - May 2012
Externally publishedYes


  • Adhesion molecules
  • Allergy
  • CCL25
  • Chemokines
  • T cells


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