Differentiation and functional analysis of human TH17 cells

• Published in: Journal of allergy and clinical immunology 2009-03, Vol.123 (3), p.588-595
• Main Authors: BURGLER, Simone, OUAKED, Nadia, BASSIN, Claudio, BASINSKI, Tomasz M, MANTEL, Pierre-Yves, SIEGMUND, Kerstin, MEYER, Norbert, AKDIS, Cezmi A, SCHMIDT-WEBER, Carsten B
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cytokines; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; Lymphocytes; Medical sciences; Methods; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Transcription factors
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2008.12.017

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 THcell subsets. Methods Naive human CD4+T cells were differentiatedin vitro, and gene expression was analyzed by means of quantitative real-time PCR, ELISA, and immunofluorescence. The function of THcell subsets was assessed by monitoring the response of primary bronchial epithelial cells in coculture experiments. Results In vitrodifferentiated TH17 cells differ from Treg and other THcells 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.