Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity.
Item Type:Journal Article
Citation:Sutton, C.E., Lalor, S.J., Sweeney, C.M., Brereton, C.F., Lavelle, E.C. and Mills, K.H.G, Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity., Immunity, 31, 2, 2009, 331-341
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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 gamma delta T cells express IL-23R and the transcription factor ROR gamma t and produce IL-17, IL-21, and IL-22 in response to IL-1 beta and IL-23, without T cell receptor engagement. IL-17-producing gamma delta T cells were found at high frequency in the brain of mice with experimental autoimmune encephalomyelitis (EAE). gamma delta T cells activated by IL-1 beta and IL-23 promoted IL-17 production by CD4(+) T cells and increased susceptibility to EAE, suggesting that gamma delta T cells act in an amplification loop for IL-1 7 production by Th17 cells. Our findings demonstrate that gamma delta T cells activated by IL-1 beta 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.
Type of material:Journal Article
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