Developmental control of integrin expression regulates Th2 effector homing

Seung Hyo Lee, Joseph E. Prince, Muhammad Rais, Farrah Kheradmand, Christie M. Ballantyne, Gabriele Weitz-Schmidt, C. Wayne Smith, David Corry

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Integrin CD18, a component of the LFA-1 complex that also includes CD11a, is essential for Th2, but not Th1, cell homing, but the explanation for this phenomenon remains obscure. In this study, we investigate the mechanism by which Th2 effector responses require the LFA-1 complex. CD11a-deficient T cells showed normal in vitro differentiation and function. However, Th2 cell- dependent allergic lung disease was markedly reduced in CD11a null mice and wild-type mice given LFA-1 inhibitors, whereas control of infection with Leishmanial major, a Th1-dependent response, was enhanced. In both disease models, recruitment of IL-4-, but not IFN-γ-secreting cells to relevant organs was impaired, as was adhesion of Th2 cells in vitro. These diverse findings were explained by the markedly reduced expression of CD29, an alternate homing integrin, on Th2, but not Th1, cells, which precludes Th2 homing in the absence of CD11a. Thus, murine Th1 and Th2 cells use distinct integrins for homing, suggesting novel opportunities for integrin-based therapeutic intervention in diverse human ailments influenced by Th2 cells.

Original languageEnglish (US)
Pages (from-to)4656-4667
Number of pages12
JournalJournal of Immunology
Volume180
Issue number7
DOIs
StatePublished - Apr 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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