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 RORγt that produced interleukin 22 (IL-22). The emergence of these IL-22-producing RORγthiNKp46+NK1.1int cells depended on RORγt 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.
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Acknowledgements
We thank M. Kist for support; M. Lucas, H. Pircher, W. Schachterle and C. Vonarbourg for critical comments on the manuscript; M. Schnare for discussions; K. Geiger and M. Follo for cell sorting; D. Littman (New York University) for Rorc(γt)GFP/+ mice; B. Stockinger (National Institute for Medical Research Mill Hill) for support and reagents; M. Kopf (Swiss Federal Institute of Technology Zürich) for Il6−/− mice on a B6 background; J.-C. Renauld (Ludwig Institute for Cancer Research Brussels) for anti-IL-22; and N. Goeppert for technical assistance. Supported by Deutsche Forschungsgemeinschaft (Di 764/2-2, GRK1104 (A.M.) and SFB620).
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S.L.S., V.L.B., A.M., K.O. and C.H. did and analyzed the experiments; C.J. generated and provided the germ-free mice and contributed to the experimental design; and A.D. and S.L.S. designed the experiments and wrote the paper.
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Sanos, S., Bui, V., Mortha, A. et al. RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22–producing NKp46+ cells. Nat Immunol 10, 83–91 (2009). https://doi.org/10.1038/ni.1684
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DOI: https://doi.org/10.1038/ni.1684
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