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


Sujino, T; London, M; Hoytema van Konijnenburg, D P; Rendon, T; Buch, T; Silva, H M; Lafaille, J J; Reis, B S; Mucida, D (2016). Tissue adaptation of regulatory and intraepithelial CD4+ T cells controls gut inflammation. Science, 352(6293):1581-1586.

Abstract

Foxp3+ regulatory T cells in peripheral tissues (pTregs) are instrumental in limiting inflammatory responses to nonself antigens. Within the intestine, pTregs are located primarily in the lamina propria, whereas intraepithelial CD4+ T cells (CD4IELs), 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 Tregs and CD4IELs. Upon migration to the epithelium,Tregs lose Foxp3 and convert to CD4IELs in a microbiota-dependent manner, an effect attributed to the loss of the transcription factor ThPOK. Finally, we demonstrate that pTregs and CD4IELs 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.

Abstract

Foxp3+ regulatory T cells in peripheral tissues (pTregs) are instrumental in limiting inflammatory responses to nonself antigens. Within the intestine, pTregs are located primarily in the lamina propria, whereas intraepithelial CD4+ T cells (CD4IELs), 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 Tregs and CD4IELs. Upon migration to the epithelium,Tregs lose Foxp3 and convert to CD4IELs in a microbiota-dependent manner, an effect attributed to the loss of the transcription factor ThPOK. Finally, we demonstrate that pTregs and CD4IELs 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.

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Contributors:K. Velinzon and N. Thomas for sorting cells and to members of the Nussenzweig lab and The Rockefeller University, S. Hemmers (Memorial Sloan Kettering Cancer Center) for generating Cd4CreER mice, A. Rogoz for outstanding technical support, V. Pedicord, and D. Esterhazy
Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Laboratory Animal Science
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2016
Deposited On:06 Sep 2016 12:53
Last Modified:06 Sep 2016 12:55
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
Funders:Leona M. and Harry B. Helmsley Charitable Trust, Japan Foundation for Applied Enzymology and Uehara Memorial Foundation, Alexandre Suerman Stipend, Royal Netherlands Academy of Sciences, and the Prince Bernhard Cultural Foundation, Deutsche Forschungsgemeinschaft 1410/1 grant, Swiss National Science Foundation 0310030-11620 grant, National Multiple Sclerosis Society, the Crohn’s & Colitis Foundation of America, the Irma T. Hirschl Award, National Institutes of Health grant NIH R01 DK093674, The Rockefeller University Bio-Imaging Resource Center is supported by the Empire State Stem Cell Fund through New York State Department of Health C023046
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1126/science.aaf3892

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