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PMID: 19029903 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells.

Nature immunology ·Vol. 10 ·No. 1 ·2009-01-00 ·Pages 83-91

Sanos SL, Bui VL, Mortha A, Oberle K, Heners C, Johner C, Diefenbach A

Abstract

The mucosal immune system of the intestine is separated from a vast array of microbes by a single layer of epithelial cells. Cues from the commensal microflora are needed to maintain epithelial homeostasis, but the molecular and cellular identities of these cues are unclear. Here we provide evidence that signals from the commensal microflora contribute to the differentiation of a lymphocyte population coexpressing stimulatory natural killer cell receptors and the transcription factor RORgammat that produced interleukin 22 (IL-22). The emergence of these IL-22-producing RORgammathiNKp46+NK1.1(int) cells depended on RORgammat expression, which indicated that these cells may have been derived from lymphoid tissue-inducer cells. IL-22 released by these cells promoted the production of antimicrobial molecules important in the maintenance of mucosal homeostasis.

MeSH Terms
Animals Antigens, Ly/immunology Bacteria/immunology Cell Differentiation Homeostasis/immunology Interleukins/biosynthesis Intestinal Mucosa/immunology,microbiology Mice Mice, Knockout Natural Cytotoxicity Triggering Receptor 1/immunology Natural Killer T-Cells/cytology,immunology Nuclear Receptor Subfamily 1, Group F, Member 3 Peyer's Patches/immunology Receptors, Retinoic Acid/genetics,physiology Receptors, Thyroid Hormone/genetics,physiology Transcription Factors/physiology
Chemicals
Antigens, Ly Interleukins Natural Cytotoxicity Triggering Receptor 1 Ncr1 protein, mouse Nuclear Receptor Subfamily 1, Group F, Member 3 Receptors, Retinoic Acid Receptors, Thyroid Hormone Rorc protein, mouse Transcription Factors interleukin-22
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Sanos Stephanie L
Institute of Medical Microbiology and Hygiene, University of Freiburg, 79104 Freiburg, Germany.
Bui Viet L
Mortha Arthur
Oberle Karin
Heners Charlotte
Johner Caroline
Diefenbach Andreas
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1684
Published
2009-01-00
Epub
2008-00-23
Pages
83-91
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC4217274
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007308 · United States
Corrections
CommentIn
PMID: 19088733
External Links
PubMed source DOI: 10.1038/ni.1684 PMC Full Text View journal details
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