Regulation of IL-17 production in human lymphocytes.
The discovery of a new lineage of helper T cells that selectively produces interleukin (IL)-17 has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. Although the factors that promote murine Th17 differentiation have been intensively examined, there has been much less information on the regulation of this cytokine in human T cells. IL-17 is readily produced by human memory T cells, which we now know exhibit distinct patterns of chemokine receptor expression and may differentiate in response to selective pathogens. Recently it has been shown that IL-1, IL-6 and IL-23 are important in driving human Th17 differentiation. However, TGFbeta-1 which is important for the differentiation of murine Th17 cells and inducible regulatory T cells (iTregs), is reportedly not required and even inhibits for human Th17 differentiation. In addition, human Th17 cells also produce other proinflammatory cytokines. Further characterization of the transcription regulation of human IL-17 expression, and the epigenetic regulation of human Il17 locus should improve our understanding the lineage commitment of human Th17 cells. Targeting the production and action of this cytokine is also likely to be beneficial therapeutically for autoinflammatory and autoimmune diseases.
Chen
Zhi
Z
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. zchen@utu.fi
O'Shea
John J
JJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000502:physiology
D020381:Interleukin-17; D053773:Transforming Growth Factor beta1