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Cell. 2015 Oct 8;163(2):381-93. doi: 10.1016/j.cell.2015.08.061. Epub 2015 Sep 24.

An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses.

Author information

1
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
2
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; The Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.
3
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, Computer Science Department, New York University, New York, NY 10003, USA; Simons Center for Data Analysis, Simons Foundation, New York, NY 10010, USA.
4
Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
5
Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, Computer Science Department, New York University, New York, NY 10003, USA; Simons Center for Data Analysis, Simons Foundation, New York, NY 10010, USA.
6
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; The Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA. Electronic address: dan.littman@med.nyu.edu.

Erratum in

  • Cell. 2016 Jan 14;164(1-2):324. Dosage error in article text.

Abstract

RORγt(+) Th17 cells are important for mucosal defenses but also contribute to autoimmune disease. They accumulate in the intestine in response to microbiota and produce IL-17 cytokines. Segmented filamentous bacteria (SFB) are Th17-inducing commensals that potentiate autoimmunity in mice. RORγt(+) T cells were induced in mesenteric lymph nodes early after SFB colonization and distributed across different segments of the gastrointestinal tract. However, robust IL-17A production was restricted to the ileum, where SFB makes direct contact with the epithelium and induces serum amyloid A proteins 1 and 2 (SAA1/2), which promote local IL-17A expression in RORγt(+) T cells. We identified an SFB-dependent role of type 3 innate lymphoid cells (ILC3), which secreted IL-22 that induced epithelial SAA production in a Stat3-dependent manner. This highlights the critical role of tissue microenvironment in activating effector functions of committed Th17 cells, which may have important implications for how these cells contribute to inflammatory disease.

PMID:
26411290
PMCID:
PMC4621768
DOI:
10.1016/j.cell.2015.08.061
[Indexed for MEDLINE]
Free PMC Article

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