The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online
doi:10.1084/jem.20072713
The Journal of Experimental Medicine, Vol. 206, No. 1, 35-41
The Rockefeller University Press, 0022-1007 $30.00
© Takatori et al.
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BRIEF DEFINITIVE REPORT

 Lymphoid tissue inducer–like cells are an innate source of IL-17 and IL-22

Hiroaki Takatori1, Yuka Kanno1, Wendy T. Watford1, Cristina M. Tato1, Greta Weiss2, Ivaylo I. Ivanov3, Dan R. Littman3, and John J. O'Shea1

1 Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892
2 University of Pennsylvania–National Institutes of Health Graduate Program, Bethesda, MD 20892
3 Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016

CORRESPONDENCE Hiroaki Takatori: takatorih{at}mail.nih.gov

The interleukin (IL) 17 family of cytokines has emerged to be critical for host defense as well as the pathogenesis of autoimmune and autoinflammatory disorders, and serves to link adaptive and innate responses. Recent studies have identified a new subset of T cells that selectively produce IL-17 (Th17 cells; Bettelli, E., T. Korn, and V.K. Kuchroo. 2007. Curr. Opin. Immunol. 19:652–657; Kolls, J.K., and A. Linden. 2004. Immunity. 21:467–476), but the regulation of IL-17 production by innate immune cells is less well understood. We report that in vitro stimulation with IL-23 induced IL-17 production by recombination activating gene (Rag) 2–/– splenocytes but not Rag2–/– common {gamma} chain–/– splenocytes. We found that a major source of IL-17 was CD4+CD3–NK1.1–CD11b–Gr1–CD11c–B220– cells, a phenotype that corresponds to lymphoid tissue inducer–like cells (LTi-like cells), which constitutively expressed the IL-23 receptor, aryl hydrocarbon receptor, and CCR6. In vivo challenge with the yeast cell wall product zymosan rapidly induced IL-17 production in these cells. Genetic deletion of signal transducer and activator of transcription 3 reduced but did not abrogate IL-17 production in LTi-like cells. Thus, it appears that splenic LTi-like cells are a rapid source of IL-17 and IL-22, which might contribute to dynamic organization of secondary lymphoid organ structure or host defense.

C.M. Tato's present address is Dept. of Discovery Research, DNAX Research Inc., Palo Alto, CA 94304.

G. Weiss's present address is National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.


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