Intestinal bacteria induce TSLP to promote mutualistic T-cell responses

Mucosal Immunol. 2013 Nov;6(6):1157-67. doi: 10.1038/mi.2013.12. Epub 2013 Mar 20.

Abstract

Thymic stromal lymphopoietin (TSLP) is constitutively expressed in the intestine and is known to regulate inflammation in models of colitis. We show that steady-state TSLP expression requires intestinal bacteria and has an important role in limiting the expansion of colonic T helper type 17 (Th17) cells. Inappropriate expansion of the colonic Th17 cells occurred in response to an entirely benign intestinal microbiota, as determined following the colonization of germ-free C57BL/6 or TSLPR(-/-) mice with the altered Schaedler flora (ASF). TSLP-TSLPR (TSLP receptor) interactions also promoted the expansion of colonic Helios(-)Foxp3(+) regulatory T cells, necessary for the control of inappropriate Th17 responses following ASF bacterial colonization. In summary, these data reveal an important role for TSLP-TSLPR signaling in promoting steady-state mutualistic T-cell responses following intestinal bacterial colonization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / immunology*
  • Cell Communication
  • Cell Proliferation
  • Cells, Cultured
  • Colitis / immunology*
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunity, Cellular
  • Immunoglobulins / metabolism
  • Immunomodulation
  • Intestines / immunology*
  • Intestines / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota / immunology
  • Receptors, Cytokine / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*
  • Thymic Stromal Lymphopoietin

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunoglobulins
  • Receptors, Cytokine
  • Tslpr protein, mouse
  • Thymic Stromal Lymphopoietin