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

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Science  24 Jun 2016:
Vol. 352, Issue 6293, pp. 1581-1586
DOI: 10.1126/science.aaf3892

Location matters for immunosuppression

In the gut, food antigens and resident microbes can trigger unwanted immune responses. Immunosuppressive cell types in the gut, such as regulatory T cells (Tregs) and intraepithelial T lymphocytes (IELs), help to keep these responses at bay. Sujino et al. report that the specific anatomical location within the gut shapes the properties of the suppressive T cell populations that reside there (see the Perspective by Colonna and Cervantes-Barragan). Using mice, they find that Tregs primarily reside in the lamina propria. Tregs migrate to the intestinal epithelium, where they convert to IELs in a process that depends on the microbiota and the loss of a specific transcription factor. Tregs and IELs also play distinct but complementary roles in suppressing intestinal inflammation.

Science, this issue p. 1581; see also p. 1515


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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