SUMMARY Although several interleukin-17 (IL-17) family members and their receptors have been recently appreciated as important regulators in inflammatory diseases, the function of other IL-17 cytokines and IL-17 receptor-like molecules is unclear. Here we show that an IL-17 cytokine family member, IL-17C, was induced in a Th17 cell-dependent autoimmune disease and was required for its pathogenesis. IL-17C bound to IL-17RE, a member of IL-17 receptor family whose full-length isoform was selectively expressed in Th17 cells and signaled via an IL-17RARE receptor complex and the downstream adaptor Act1. IL-17C-IL-17RE induced the expression of a nuclear IkappaB family member, IκBζ, in Th17 cells to potentiate the Th17 cell response. Thus, our work has identified a cytokine-receptor pair with important function in regulating proinflammatory responses. This pathway may be targeted to treat autoimmune diseases.

Objective. To explore whether there are extrinsic factors that impair the suppressive function of CD4؉,CD25؉ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE).Methods. We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4؉,CD25؉, FoxP3؉ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-␣ (IFN␣) in supernatants from the function assays were determined with an IFN-stimulated response element-luciferase reporter assay.Results. The percentage of CD4؉,CD25؉, FoxP3؉ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean ؎ SEM 9.11 ؎ 0.73% versus 4.78 ؎ 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4؉,CD25؉ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4؉,CD25؉ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFN␣ derived from SLE patient APCs.Conclusion. We suggest that blockade of Treg cell-mediated suppression by IFN␣-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease.

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Microbes are key components of aquatic ecosystems and play crucial roles in global biogeochemical cycles. However, the spatiotemporal dynamics of planktonic microbial community composition in riverine ecosystems are still poorly understood. In this study, we used denaturing gradient gel electrophoresis of PCR-amplified 16S and 18S rRNA gene fragments and multivariate statistical methods to explore the spatiotemporal patterns and driving factors of planktonic bacterial and microbial eukaryotic communities in the subtropical Jiulong River, southeast China. Both bacterial and microbial eukaryotic communities varied significantly in time and were spatially structured according to upper stream, middle-lower stream and estuary. Among all the environmental factors measured, water temperature, conductivity, PO4-P and TN/TP were best related to the spatiotemporal distribution of bacterial community, while water temperature, conductivity, NOx-N and transparency were closest related to the variation of eukaryotic community. Variation partitioning, based on partial RDA, revealed that environmental factors played the most important roles in structuring the microbial assemblages by explaining 11.3% of bacterial variation and 17.5% of eukaryotic variation. However, pure spatial factors (6.5% for bacteria and 9.6% for eukaryotes) and temporal factors (3.3% for bacteria and 5.5% for eukaryotes) also explained some variation in microbial distribution, thus inherent spatial and temporal variation of microbial assemblages should be considered when assessing the impact of environmental factors on microbial communities.