SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses

Camille Knosp, Helen Carroll, Joanne Elliott, Sean P. Saunders, H.J. Nel, S. Amu, J. Pratt, Shaun Spence, Emma Doran, Nicola Cooke, Ruaidhri Jackson, Jonathan Swift, Denise Fitzgerald, Liam Heaney, P.G. Fallon, Adrien Kissenpfennig, James Johnston

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The incidence of allergy and asthma in developed countries is on the increase and this trend looks likely to continue. CD4(+) T helper 2 (Th2) cells are major drivers of these diseases and their commitment is controlled by cytokines such as interleukin 4, which are in turn regulated by the suppressor of cytokine signaling (SOCS) proteins. We report that SOCS2(-/-) CD4(+) T cells show markedly enhanced Th2 differentiation. SOCS2(-/-) mice, as well as RAG1(-/-) mice transferred with SOCS2(-/-) CD4(+) T cells, exhibit elevated type 2 responses after helminth antigen challenge. Moreover, in in vivo models of atopic dermatitis and allergen-induced airway inflammation, SOCS2(-/-) mice show significantly elevated IgE, eosinophilia, type 2 responses, and inflammatory pathology relative to wild-type mice. Finally, after T cell activation, markedly enhanced STAT6 and STAT5 phosphorylation is observed in SOCS2(-/-) T cells, whereas STAT3 phosphorylation is blunted. Thus, we provide the first evidence that SOCS2 plays an important role in regulating Th2 cell expansion and development of the type 2 allergic responses.

Original languageEnglish
Pages (from-to)1523-1531
Number of pages9
JournalJournal of Experimental Medicine
Volume208
Issue number7
Early online date06 Jun 2011
DOIs
Publication statusPublished - 04 Jul 2011

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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