Interleukin-2, Interleukin-7, T cell-mediated autoimmunity, and N-glycosylation

Ann N Y Acad Sci. 2012 Apr;1253:49-57. doi: 10.1111/j.1749-6632.2011.06391.x. Epub 2012 Jan 30.

Abstract

T cell activation and self-tolerance are tightly regulated to provide effective host defense against foreign pathogens while deflecting inappropriate autoimmune responses. Golgi Asn (N)-linked protein glycosylation coregulates homeostatic set points for T cell growth, differentiation, and self-tolerance to influence risk of autoimmune disorders such as multiple sclerosis (MS). Human autoimmunity is a complex trait that develops from intricate and poorly understood interactions between an individual's genetics and their environmental exposures. Recent evidence from our group suggests that in MS, additive and/or epistatic interactions between multiple genetic and environmental risk factors combine to dysregulate a common biochemical pathway, namely Golgi N-glycosylation. Here, we review the multiple regulatory mechanisms controlling N-glycan branching in T cells and autoimmunity, focusing on recent data implicating a critical role for interleukin-2 (IL-2) and IL-7 signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmunity*
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / immunology
  • Glycosylation
  • Humans
  • Interleukin-2 / chemistry
  • Interleukin-2 / immunology*
  • Interleukin-7 / chemistry
  • Interleukin-7 / immunology*
  • Lymphocyte Activation
  • Multiple Sclerosis / etiology
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / immunology
  • Risk Factors
  • Self Tolerance
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human
  • IL2 protein, human
  • IL7 protein, human
  • Interleukin-2
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Receptors, Interleukin-7
  • MGAT1 protein, human
  • N-Acetylglucosaminyltransferases