RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells.
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.
Sanos
Stephanie L
SL
Institute of Medical Microbiology and Hygiene, University of Freiburg, 79104 Freiburg, Germany.
Bui
Viet L
VL
Mortha
Arthur
A
Oberle
Karin
K
Heners
Charlotte
C
Johner
Caroline
C
Diefenbach
Andreas
A
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D001419:Bacteria / Q000276:immunology; D002454:Cell Differentiation; D006706:Homeostasis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010581:Peyer's Patches / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D000097043:Interleukin-22
D000950:Antigens, Ly; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D000097043:Interleukin-22; C118384:Ncr1 protein, mouse; C539901:Rorc protein, mouse