The Effect of Inflammatory Cytokines on the Differentiation of Th17 Cells in Human Peripheral Blood / 대한류마티스학회지

ABSTRACT

OBJECTIVE: IL-17-producing T cells (Th17 cells) have been identified as a distinct lineage of CD4+ T helper cells in mice. Since this discovery, many efforts have been made to investigate the characteristics and the role of human Th17 cells and the factors involved in their differentiation. This study was undertaken to assess the effects of cytokines and stimulatory conditions on the differentiation of human CD4+ T cells into Th17 cells. METHODS: Peripheral blood CD4+ T cells were isolated from healthy humans and then these cells were cultured with using various stimulatory conditions. The Th17 cells and regulatory T (Treg) cells were detected by flow cytometry (FACs). The related gene expressions of cytokines, transcription factors and chemokine receptors were determined by ELISA and RT-PCR. RESULTS: In the presence of inflammatory cytokines, TNFa and IL-1b, the human CD4+ T cells rapidly produced IL-17 in response to anti-CD3/anti-CD28 stimulation, whereas, with anti-CD3/anti-CD28 stimulation alone, the CD4+ T cells expressed low levels of IL-17. TNFa and IL-1b were also important inducers of IL-22 production. IL-6 and IL-23 up-regulated the RORgammat, CCR4 and CCR6 expressions in the human CD4+ T cells. In response to TGF-b and IL-2, the human CD4+ T cells were rapidly induced to express FoxP3, IL-10 and CCR7, as compared with anti-CD3/anti-CD28 stimulation alone. CONCLUSION: The effect of inflammatory cytokines on the differentiation of human Th17 cells may help us to understand their pathogenic role. Moreover, the differential expression of chemokine receptors and transcription factors of the subsets of CD4+ T cells with the different features of Th17 and Treg, may raise new issues concerning the pathogenesis of autoimmune inflammatory diseases.