T<inf>H</inf>9 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 Kaplan

Research output: Contribution to journalArticle

60 Citations (Scopus)

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

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Mast Cells
Interleukin-9
Inflammation
T-Lymphocytes
Natural Killer T-Cells
Adoptive Transfer
Peptide Hydrolases
Lymphocytes
Interleukin-13
Ovalbumin
Eosinophils
Pneumonia
Cell Count
Cytokines

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

Cite this

T<inf>H</inf>9 cells are required for tissue mast cell accumulation during allergic inflammation. / Sehra, Sarita; Yao, Weiguo; Nguyen, Evelyn T.; Glosson-Byers, Nicole L.; Akhtar, Nahid; Zhou, Baohua; Kaplan, Mark.

In: Journal of Allergy and Clinical Immunology, Vol. 136, No. 2, 01.08.2015, p. 433-440.e1.

Research output: Contribution to journalArticle

Sehra, Sarita ; Yao, Weiguo ; Nguyen, Evelyn T. ; Glosson-Byers, Nicole L. ; Akhtar, Nahid ; Zhou, Baohua ; Kaplan, Mark. / T<inf>H</inf>9 cells are required for tissue mast cell accumulation during allergic inflammation. In: Journal of Allergy and Clinical Immunology. 2015 ; Vol. 136, No. 2. pp. 433-440.e1.
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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 TH9 cells in promoting mast cell accumulation in models of allergic lung inflammation. Methods Adoptive transfer of ovalbumin-specific TH2 and TH9 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 TH9 cells had significantly higher mast cell accumulation and expression of mast cell proteases compared with control or TH2 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+ T cells, but not natural killer T cells or innate lymphoid cells, suggesting a TH cell-dependent phenotype. Rag1-/- 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 TH9 cells are a major source of IL-9 in models of allergic inflammation and play an important role in mast cell accumulation and activation.",
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AU - Sehra, Sarita

AU - Yao, Weiguo

AU - Nguyen, Evelyn T.

AU - Glosson-Byers, Nicole L.

AU - Akhtar, Nahid

AU - Zhou, Baohua

AU - Kaplan, Mark

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N2 - 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 TH9 cells in promoting mast cell accumulation in models of allergic lung inflammation. Methods Adoptive transfer of ovalbumin-specific TH2 and TH9 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 TH9 cells had significantly higher mast cell accumulation and expression of mast cell proteases compared with control or TH2 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+ T cells, but not natural killer T cells or innate lymphoid cells, suggesting a TH cell-dependent phenotype. Rag1-/- 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 TH9 cells are a major source of IL-9 in models of allergic inflammation and play an important role in mast cell accumulation and activation.

AB - 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 TH9 cells in promoting mast cell accumulation in models of allergic lung inflammation. Methods Adoptive transfer of ovalbumin-specific TH2 and TH9 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 TH9 cells had significantly higher mast cell accumulation and expression of mast cell proteases compared with control or TH2 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+ T cells, but not natural killer T cells or innate lymphoid cells, suggesting a TH cell-dependent phenotype. Rag1-/- 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 TH9 cells are a major source of IL-9 in models of allergic inflammation and play an important role in mast cell accumulation and activation.

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