title: Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity.
abstract: Th17 cells, CD4(+) T cells that secrete interleukin-17 (IL-17), are pathogenic in autoimmune diseases and their development and expansion is driven by the cytokines IL-6, TGF-beta, IL-21, IL-1, and IL-23. However, there are also innate sources of IL-17. Here, we show that gammadelta T cells express IL-23R and the transcription factor RORgammat and produce IL-17, IL-21, and IL-22 in response to IL-1beta and IL-23, without T cell receptor engagement. IL-17-producing gammadelta T cells were found at high frequency in the brain of mice with experimental autoimmune encephalomyelitis (EAE). gammadelta T cells activated by IL-1beta and IL-23 promoted IL-17 production by CD4(+) T cells and increased susceptibility to EAE, suggesting that gammadelta T cells act in an amplification loop for IL-17 production by Th17 cells. Our findings demonstrate that gammadelta T cells activated by IL-1beta and IL-23 are an important source of innate IL-17 and IL-21 and provide an alternative mechanism whereby IL-1 and IL-23 may mediate autoimmune inflammation.
authors.affiliation: Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Sutton
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lalor
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Sweeney
authors.forename: Corinna F
authors.initials: CF
authors.lastname: Brereton
authors.forename: Ed C
authors.initials: EC
authors.lastname: Lavelle
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
mesh_terms: D000818:Animals; D015551:Autoimmunity; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22; D000098546:Interleukin-21
chemical_list: D017252:CD3 Complex; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D007378:Interleukins; D008070:Lipopolysaccharides; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D053722:Receptors, Interleukin-17; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000097043:Interleukin-22; D000098546:Interleukin-21; C539901:Rorc protein, mouse; C528688:interleukin-23 receptor, mouse