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

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

Author information

1
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
2
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA. Laboratory of Translational Immunology, University Medical Center Utrecht, the Netherlands.
3
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
4
Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
5
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA. breis@rockefeller.edu mucida@rockefeller.edu.

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.

Comment in

PMID:
27256884
PMCID:
PMC4968079
DOI:
10.1126/science.aaf3892
[Indexed for MEDLINE]
Free PMC Article

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