Effector CD4 T cells with progenitor potential mediate chronic intestinal inflammation

J Exp Med. 2018 Jul 2;215(7):1803-1812. doi: 10.1084/jem.20172335. Epub 2018 Jun 18.

Abstract

Dysregulated CD4 T cell responses are causally linked to autoimmune and chronic inflammatory disorders, yet the cellular attributes responsible for maintaining the disease remain poorly understood. Herein, we identify a discrete population of effector CD4 T cells that is able to both sustain and confer intestinal inflammation. This subset of pathogenic CD4 T cells possesses a unique gene signature consistent with self-renewing T cells and hematopoietic progenitor cells, exhibits enhanced survival, and continually seeds the terminally differentiated IFNγ-producing cells in the inflamed intestine. Mechanistically, this population selectively expresses the glycosyltransferase ST6Gal-I, which is required for optimal expression of the stemness-associated molecule TCF1 by effector CD4 T cells. Our findings indicate that the chronicity of T cell-mediated inflammation is perpetuated by specific effector CD4 T cells with stem-like properties.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Self Renewal
  • Cell Survival
  • Chronic Disease
  • Colitis / immunology
  • Colitis / pathology
  • Gene Expression Profiling
  • Hepatocyte Nuclear Factor 1-alpha / metabolism
  • Inflammation / immunology*
  • Inflammation / pathology
  • Interferon-gamma / metabolism
  • Intestines / pathology*
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • N-Acetylneuraminic Acid / metabolism
  • Sialyltransferases / metabolism
  • Stem Cells / immunology*
  • beta-D-Galactoside alpha 2-6-Sialyltransferase

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Interferon-gamma
  • Sialyltransferases
  • N-Acetylneuraminic Acid
  • beta-D-Galactoside alpha 2-6-Sialyltransferase