title: Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22.
abstract: 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.
authors.affiliation: Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. takatorih@mail.nih.gov
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takatori
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: Wendy T
authors.initials: WT
authors.lastname: Watford
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Tato
authors.forename: Greta
authors.initials: G
authors.lastname: Weiss
authors.forename: Ivaylo I
authors.initials: II
authors.lastname: Ivanov
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D007107:Immune System / Q000166:cytology / Q000378:metabolism*; D007113:Immunity, Innate / Q000276:immunology*; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D054399:Receptors, CCR6 / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology; D000097043:Interleukin-22
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D053631:Interleukin Receptor Common gamma Subunit; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; D054399:Receptors, CCR6; D018123:Receptors, Interleukin; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D050796:STAT3 Transcription Factor; D015054:Zymosan; D000097043:Interleukin-22; C498126:CCR6 protein, mouse; C499308:Rag2 protein, mouse; C539901:Rorc protein, mouse; C494087:Stat3 protein, mouse; C528688:interleukin-23 receptor, mouse