An Inflammatory Lineage

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Science  11 Nov 2005:
Vol. 310, Issue 5750, pp. 945
DOI: 10.1126/science.310.5750.945a

Helper CD4+ T (TH) cells are traditionally divided into two principal lineages: interleukin-4 (IL-4)/IL-5-producing TH2 cells, which are associated with allergic and antiparasitic responses, and TH1 cells that produce inflammatory cytokines, principally interferon-γ (INF-γ). However, the expression of the cytokine IL-17 by a relatively small subset of CD4+ T cells and its association with inflammation has suggested that this may define a TH1 sublineage.

Now, Harrington et al. and Park et al. provide evidence that IL-17-producing CD4+ T cells may represent a distinct T-helper population altogether, the development of which is coordinately regulated with those of TH1 and TH2 cells. Both studies confirmed the dependence of IL-17 expression on signaling through the receptor for the cytokine IL-23 and demonstrated that this was independent of the signals and transcriptional pathways responsible for IFN-γ and IL-4 production. Furthermore, both of these T-helper cytokines were found to inhibit IL-17 expression in naïve T cells—as opposed to differentiated IL-17+ T cells—suggesting a dominant role in cross-regulation during early T cell priming. Given the clear association of IL-17 with tissue inflammatory responses, the strict management of TH17 cell differentiation may represent a central checkpoint in preventing immune pathologies such as those seen in autoimmune diseases. — SJS

Nat. Immunol. 6, 1123; 1133 (2005).

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