T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis

Mucosal Immunol. 2016 Nov;9(6):1487-1499. doi: 10.1038/mi.2016.5. Epub 2016 Feb 17.

Abstract

The transcription factor T-bet is highly expressed by Th cells isolated from the inflamed intestine of Crohn's disease patients, and has been regarded a critical driver of murine T cell-induced colitis. However, we show here that T-bet expression by Th cells is not required for the manifestation of T-cell-induced colitis in the presence of segmented filamentous bacteria and Helicobacter hepaticus. T-bet expression by Th cells controls their survival and localization, their repertoire of chemokine and chemokine receptor expression, the accumulation of monocytes and macrophages in the inflamed colon, and their differentiation to the M1 type, i.e., type 1 inflammation. Nevertheless, T-bet-deficient Th cells efficiently induce colitis, as reflected by weight loss, diarrhea, and colon histopathology. T-bet-deficient Th cells differentiate into Th1/17 cells, able to express IFN-γ and IL-17A upon restimulation. While neutralization of IL-17A exacerbated colitis induced by wild-type or T-bet-deficient Th cells, neutralization of IFN-γ completely abolished colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Colitis / etiology*
  • Colitis / pathology
  • Disease Models, Animal
  • Gene Expression*
  • Inflammation / etiology*
  • Inflammation / pathology
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / metabolism
  • Lymphocyte Count
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Monocytes / immunology
  • Monocytes / metabolism
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Interleukin-17
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interferon-gamma