title: Tissue adaptation of regulatory and intraepithelial CD4⁺ T cells controls gut inflammation.
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.
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Sujino
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Mariya
authors.initials: M
authors.lastname: London
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA. Laboratory of Translational Immunology, University Medical Center Utrecht, the Netherlands.
authors.forename: David P
authors.initials: DP
authors.lastname: Hoytema van Konijnenburg
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Tomiko
authors.initials: T
authors.lastname: Rendon
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buch
authors.affiliation: Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Hernandez M
authors.initials: HM
authors.lastname: Silva
authors.affiliation: Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lafaille
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA. breis@rockefeller.edu mucida@rockefeller.edu.
authors.forename: Bernardo S
authors.initials: BS
authors.lastname: Reis
authors.affiliation: Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA. breis@rockefeller.edu mucida@rockefeller.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
mesh_terms: D000818:Animals; D002465:Cell Movement; D058948:Cell Tracking; D003092:Colitis; D051543:Hepatocyte Nuclear Factor 3-gamma; D007413:Intestinal Mucosa; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064307:Microbiota; D050378:T-Lymphocytes, Regulatory; D014157:Transcription Factors
chemical_list: D051543:Hepatocyte Nuclear Factor 3-gamma; D014157:Transcription Factors; C496506:Foxa3 protein, mouse; C497211:Zbtb7b protein, mouse