TH9 cells are required for tissue mast cell accumulation during allergic inflammation

Sarita Sehra, Weiguo Yao, Evelyn T. Nguyen, Nicole L. Glosson-Byers, Nahid Akhtar, Baohua Zhou, Mark H. Kaplan

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Background IL-9 is important for the growth and survival of mast cells. IL-9 is produced by T cells, natural killer T cells, mast cells, eosinophils, and innate lymphoid cells, although the cells required for mast cell accumulation during allergic inflammation remain undefined. Objective We sought to elucidate the role of T<inf>H</inf>9 cells in promoting mast cell accumulation in models of allergic lung inflammation. Methods Adoptive transfer of ovalbumin-specific T<inf>H</inf>2 and T<inf>H</inf>9 cells was used to assess the ability of each subset to mediate mast cell accumulation in tissues. Mast cell accumulation was assessed in wild-type mice and mice with PU.1-deficient T cells subjected to acute and chronic models of allergic inflammation. Results Adoptive transfer experiments demonstrated that recipients of T<inf>H</inf>9 cells had significantly higher mast cell accumulation and expression of mast cell proteases compared with control or T<inf>H</inf>2 recipients. Mast cell accumulation was dependent on IL-9, but not IL-13, a cytokine required for many aspects of allergic inflammation. In models of acute and chronic allergic inflammation, decreased IL-9 levels in mice with PU.1-deficient T cells corresponded to diminished tissue mast cell numbers and expression of mast cell proteases. Mice with PU.1-deficient T cells have defects in IL-9 production from CD4<sup>+</sup> T cells, but not natural killer T cells or innate lymphoid cells, suggesting a T<inf>H</inf> cell-dependent phenotype. Rag1<sup>-/-</sup> mice subjected to a chronic model of allergic inflammation displayed reduced mast cell infiltration comparable with accumulation in mice with PU.1-deficient T cells, emphasizing the importance of IL-9 produced by T cells in mast cell recruitment. Conclusion T<inf>H</inf>9 cells are a major source of IL-9 in models of allergic inflammation and play an important role in mast cell accumulation and activation.

Original languageEnglish (US)
Pages (from-to)433-440.e1
JournalJournal of Allergy and Clinical Immunology
Volume136
Issue number2
DOIs
StatePublished - Aug 1 2015

Keywords

  • allergic inflammation
  • mast cells
  • PU.1
  • T<inf>H</inf>2 cells
  • T<inf>H</inf>9 cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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