TGF-β1 Suppresses IL-33-Induced Mast Cell Function

J Immunol. 2017 Aug 1;199(3):866-873. doi: 10.4049/jimmunol.1601983. Epub 2017 Jun 21.


TGF-β1 is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGF-β1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGF-β on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGF-β1, β2, or β3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13, and MCP-1 in a concentration-dependent manner. TGF-β1 inhibited IL-33-mediated Akt and ERK phosphorylation as well as NF-κB- and AP-1-mediated transcription. These effects were functionally important, as TGF-β1 injection suppressed IL-33-induced systemic cytokines in vivo and inhibited IL-33-mediated cytokine release from human mast cells. TGF-β1 also suppressed the combined effects of IL-33 and IgE-mediated activation on mouse and human mast cells. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGF-β1 on IgE-mediated activation, demonstrate that TGF-β1 can provide broad inhibitory signals to activated mast cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Humans
  • Immunoglobulin E / immunology
  • Interleukin-33 / immunology*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Lymphocyte Activation / drug effects
  • MAP Kinase Signaling System / drug effects
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mice
  • NF-kappa B / genetics
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, IgE / immunology
  • Transcription Factor AP-1 / genetics
  • Transforming Growth Factor beta1 / pharmacology
  • Transforming Growth Factor beta1 / physiology*
  • Transforming Growth Factor beta3 / pharmacology


  • Cytokines
  • IL33 protein, human
  • Interleukin-33
  • Interleukin-6
  • NF-kappa B
  • Receptors, IgE
  • Transcription Factor AP-1
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta3
  • Immunoglobulin E
  • Proto-Oncogene Proteins c-akt