Tissue adaptation of regulatory and intraepithelial CD4⁺ T cells controls gut inflammation

Science. 2016 Jun 24;352(6293):1581-6. doi: 10.1126/science.aaf3892. Epub 2016 Jun 2.

Abstract

Foxp3(+) regulatory T cells in peripheral tissues (pT(regs)) are instrumental in limiting inflammatory responses to nonself antigens. Within the intestine, pT(regs) are located primarily in the lamina propria, whereas intraepithelial CD4(+) T cells (CD4(IELs)), which also exhibit anti-inflammatory properties and depend on similar environmental cues, reside in the epithelium. Using intravital microscopy, we show distinct cell dynamics of intestinal T(regs) and CD4(IELs) Upon migration to the epithelium, T(regs) lose Foxp3 and convert to CD4(IELs) in a microbiota-dependent manner, an effect attributed to the loss of the transcription factor ThPOK. Finally, we demonstrate that pT(regs) and CD4(IELs) perform complementary roles in the regulation of intestinal inflammation. These results reveal intratissue specialization of anti-inflammatory T cells shaped by discrete niches of the intestine.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement
  • Cell Tracking
  • Colitis
  • Hepatocyte Nuclear Factor 3-gamma
  • Intestinal Mucosa
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microbiota
  • T-Lymphocytes, Regulatory
  • Transcription Factors

Substances

  • Foxa3 protein, mouse
  • Th-POK protein, mouse
  • Transcription Factors
  • Hepatocyte Nuclear Factor 3-gamma