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Interleukin-1 and IL-23 Induce Innate IL-17 Production from γδ T Cells, Amplifying Th17 Responses and Autoimmunity

2009; Cell Press; Volume: 31; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2009.08.001

1097-4180

Caroline E. Sutton, Stephen J. Lalor, Cheryl Sweeney, Corinna F. Brereton, Ed C. Lavelle, Kingston H. G. Mills,

Immunodeficiency and Autoimmune Disorders

Summary 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-β, IL-21, IL-1, and IL-23. However, there are also innate sources of IL-17. Here, we show that γδ T cells express IL-23R and the transcription factor RORγt and produce IL-17, IL-21, and IL-22 in response to IL-1β and IL-23, without T cell receptor engagement. IL-17-producing γδ T cells were found at high frequency in the brain of mice with experimental autoimmune encephalomyelitis (EAE). γδ T cells activated by IL-1β and IL-23 promoted IL-17 production by CD4 + T cells and increased susceptibility to EAE, suggesting that γδ T cells act in an amplification loop for IL-17 production by Th17 cells. Our findings demonstrate that γδ T cells activated by IL-1β 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.