IL-21 and TGF-bold beta are required for differentiation of human T sub(H)17 cells
The recent discovery of CD4 super(+) T cells characterized by secretion of interleukin (IL)-17 (T sub(H)17 cells) and the naturally occurring regulatory FOXP3 super(+) CD4 T cell (nT sub(reg)) has had a major impact on our understanding of immune processes not readily explained by the T sub(H)1/T su...
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Veröffentlicht in: | Nature 2008-07, Vol.454 (7202), p.350-352 |
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Zusammenfassung: | The recent discovery of CD4 super(+) T cells characterized by secretion of interleukin (IL)-17 (T sub(H)17 cells) and the naturally occurring regulatory FOXP3 super(+) CD4 T cell (nT sub(reg)) has had a major impact on our understanding of immune processes not readily explained by the T sub(H)1/T sub(H)2 paradigm. T sub(H)17 and nT sub(reg) cells have been implicated in the pathogenesis of human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and psoriasis. Our recent data and the work of others demonstrated that transforming growth factor-beta (TGF-beta) and IL-6 are responsible for the differentiation of naive mouse T cells into T sub(H)17 cells, and it has been proposed that IL-23 may have a critical role in stabilization of the T sub(H)17 phenotype. A second pathway has been discovered in which a combination of TGF-beta and IL-21 is capable of inducing differentiation of mouse T sub(H)17 cells in the absence of IL-6. However, TGF-beta and IL-6 are not capable of differentiating human T sub(H)17 cells and it has been suggested that TGF-beta may in fact suppress the generation of human T sub(H)17 cells. Instead, it has been recently shown that the cytokines IL-1beta, IL-6 and IL-23 are capable of driving IL-17 secretion in short-term CD4 super(+) T cell lines isolated from human peripheral blood, although the factors required for differentiation of naive human CD4 to T sub(H)17 cells are still unknown. Here we confirm that whereas IL-1beta and IL-6 induce IL-17A secretion from human central memory CD4 super(+) T cells, TGF- beta and IL-21 uniquely promote the differentiation of human naive CD4 super(+) T cells into T sub(H)17 cells accompanied by expression of the transcription factor RORC2. These data will allow the investigation of this new population of T sub(H)17 cells in human inflammatory disease. |
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ISSN: | 0028-0836 1476-4679 |
DOI: | 10.1038/nature07021 |