SOCS2 Regulates T Helper Type 2 Differentiation and the Generation of Type 2 Allergic Responses

J Exp Med. 2011 Jul 4;208(7):1523-31. doi: 10.1084/jem.20101167. Epub 2011 Jun 6.

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 RAG-1(-/-) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Helminth / administration & dosage
  • Asthma / etiology
  • Asthma / immunology
  • Base Sequence
  • Cell Differentiation / immunology
  • Dermatitis, Atopic / etiology
  • Dermatitis, Atopic / immunology
  • Disease Models, Animal
  • Humans
  • Hypersensitivity / classification
  • Hypersensitivity / etiology*
  • Hypersensitivity / immunology*
  • Hypersensitivity / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • STAT Transcription Factors / metabolism
  • Suppressor of Cytokine Signaling Proteins / deficiency
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / immunology*
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Th2 Cells / cytology*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • Antigens, Helminth
  • Interleukins
  • RNA, Messenger
  • STAT Transcription Factors
  • Socs2 protein, mouse
  • Suppressor of Cytokine Signaling Proteins