Fyn Plays a Pivotal Role in Fetomaternal Tolerance Through Regulation of Th17 Cells

Am J Reprod Immunol. 2016 May;75(5):569-79. doi: 10.1111/aji.12498. Epub 2016 Feb 19.

Abstract

Problem: Spontaneous abortion is a poorly understood phenomenon, although fetomaternal intolerance is known to play an important role in its pathogenesis. The tyrosine-specific phosphotransferase Fyn has been reported as a significant regulator in immune response. However, its role in fetomaternal immune tolerance and contribution to spontaneous abortion remains unclear.

Methods of study: Fyn expression was evaluated at the fetomaternal interface of normal pregnant and abortion-prone mice, as well as in decidual tissue obtained from normal human pregnancies and idiopathic miscarriages. A Fyn inhibitor was administrated into the LPS-induced abortion mice to investigate the variation of embryo resorption and local immunity.

Results: Fyn expression fluctuated with the progress of normal pregnancy and was elevated in abortion-prone mice and patients with recurrent spontaneous abortion. The Fyn inhibitor reversed LPS-induced embryo absorption and aberrant inflammatory status including redundant expression of IRF4 and increased proportion of Th17 cells.

Conclusion: Fyn is confirmed as a negative regulator in fetomaternal immune tolerance, through promoting Th17 cell expansion and proinflammatory factors expression.

Keywords: Immunoregulation; T cells; protein tyrosine kinase; spontaneous abortion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / immunology*
  • Adult
  • Animals
  • Cells, Cultured
  • Decidua / physiology*
  • Disease Models, Animal
  • Female
  • Humans
  • Immune Tolerance
  • Interferon Regulatory Factors / metabolism*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Pregnancy
  • Proto-Oncogene Proteins c-fyn / genetics
  • Proto-Oncogene Proteins c-fyn / metabolism*
  • Th17 Cells / immunology*

Substances

  • Interferon Regulatory Factors
  • interferon regulatory factor-4
  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn