Differentiation and functional analysis of human TH17 cells

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Abstract

Background: TH17 cells are of pathologic relevance in autoimmune disorders and presumably also in allergy and asthma. Regulatory T (Treg) cells, in contrast, suppress inflammatory and allergen-driven responses. Despite these disparate functions, both T-cell subsets have been shown to be dependent on TGF-β for their development. Objective: The aim of the study was to analyze the differentiation and function of human TH17 cells in comparison with other TH cell subsets. Methods: Naive human CD4+ T cells were differentiated in vitro, and gene expression was analyzed by means of quantitative real-time PCR, ELISA, and immunofluorescence. The function of TH cell subsets was assessed by monitoring the response of primary bronchial epithelial cells in coculture experiments. Results: In vitro differentiated TH17 cells differ from Treg and other TH cells in their potency to induce IL-6 and IL-1β expression in primary bronchial epithelial cells. TGF-β, IL-1β, IL-6, and IL-23 are necessary during TH17 cell differentiation to acquire these functions, including IL-17 production. In contrast, TGF-β alone is necessary and sufficient to induce the transcription factor RORC2. This transcription factor, previously thought to be specific for TH17 cells, is also expressed in Treg cells, CD25+ cells, cytotoxic T cells, and natural killer T cells. Conclusion: This study demonstrates mechanisms of differentiation to human TH17 cells, a subset that effectively and uniquely modulates the function of primary bronchial epithelial cells. © 2009 American Academy of Allergy, Asthma & Immunology.

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Burgler, S., Ouaked, N., Bassin, C., Basinski, T. M., Mantel, P. Y., Siegmund, K., … Schmidt-Weber, C. B. (2009). Differentiation and functional analysis of human TH17 cells. Journal of Allergy and Clinical Immunology, 123(3). https://doi.org/10.1016/j.jaci.2008.12.017

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