Immunology IL-2 Antagonizes Th17 Differentiation

Elizabeth M. Adler

Science's STKE, AAAS, Washington, DC 20005, USA

T helper 17 (Th17) cells are a recently identified subset of effector T cells that produce IL-17, a cytokine implicated in various autoimmune disorders as well as (more beneficially) in the defense against extracellular bacteria. Laurence et al. found that when naïve CD4⁺ T cells were stimulated with antibodies and cultured under conditions designed to promote differentiation into Th17 cells [medium containing interleukin-6 (IL-6), transforming growth factor (TGF)-1, and blocking antibodies directed against IL-4 and interferon-], addition of IL-2 led to a dose-dependent decrease in the proportion of cells producing IL-17. In contrast, antibodies to IL-2 (which is produced by activated T cells) increased the proportion of IL-17-producing cells. T cells from mice lacking the gene encoding IL-2 (Il2^–/– mice) generated a greater percentage of IL-17-producing cells than did T cells from wild-type mice, and Il2^–/– mice had increased serum concentrations of IL-17 and a greater proportion of IL-17-positive cells in peripheral lymph nodes. Decreased abundance of STAT3 (signal transducer and activator of transcription 3, which is activated by IL-6) was associated with a decrease in the proportion of Th17 cells and of the expression of RORT messenger RNA, which encodes a nuclear receptor required for Th17 differentiation. Deletion of STAT5 (which is activated by IL-2), however, promoted Th17 differentiation. Moreover, STAT5 bound to the Il-17 promoter, suggesting that it might inhibit Il-17 transcription directly. Thus, in contrast to its well-established roles of stimulating T cell proliferation and differentiation, IL-2--once known as T cell growth factor--appears to attenuate Th17 differentiation. Stockinger provides thoughtful commentary.

A. Laurence, C. M. Tato, T. S. Davidson, Y. Kanno, Z. Chen, Z. Yao, R. B. Blank, F. Meylan, R. Siegel, L. Hennighausen, E. M. Shevach, J. J. O'Shea, Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26, 371-381 (2007). [PubMed]

B. Stockinger, Good for goose, but not for gander: IL-2 interferes with Th17 differentiation. Immunity 26, 278-279 (2007). [PubMed]

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