Increased Th22 cells are independently associated with Th17 cells in type 1 diabetes
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ORIGINAL ARTICLE
Increased Th22 cells are independently associated with Th17 cells in type 1 diabetes Xinyu Xu • Shuai Zheng • Fan Yang • Yun Shi • Yong Gu • Heng Chen • Mei Zhang Tao Yang
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Received: 11 June 2013 / Accepted: 30 July 2013 Ó Springer Science+Business Media New York 2013
Abstract Type 1 diabetes (T1D) is perceived as an autoimmune disease caused by T cell-mediated destruction of the insulin-producing pancreatic b cells. However, the number of inflammatory T cells in blood, as well as the relative importance of each cell type is unclear. Forty-two patients with T1D and 30 controls were enrolled. Circulating primary CD4? or CD8? T cells were quantified with 5-color flow cytometry. Serum IL-22 and IL-17 levels were examined by ELISA. Serum autoantibodies were measured by radio-binding assays, using 35S-labeled glutamic acid decarboxylase-65 (GAD65), protein tyrosine phosphatase-2 (IA-2), and zinc transporter 8 (ZnT8). Th17–Th22 and Tc1– Tc17 were significantly elevated in patients with T1D compared to control subjects, while there were no significant differences in Th1 cells. The levels of these T cells in different stages of T1D were investigated. Th22 cells showed a positive correlation with Th17 cells in T1D patients. However, we did not find any correlation between IL-17 and IL22 in sera. Autoantibodies were not significantly different between patients with early T1D and those who have had it for a longer duration. This study indicates that Th22 may contribute to the pathogenesis of T1D. Blockade of Th22 cells might be of clinical profit in T1D patients. Keywords Th22 cell
T1D Th cell Tc cell Th17 cell
X. Xu S. Zheng F. Yang Y. Shi Y. Gu H. Chen M. Zhang T. Yang (&) Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 300 Guangzhou Road, Nanjing 210029, Jiangsu, China e-mail: [email protected]
Introduction Type 1 diabetes (T1D) occurs as a consequence of a breakdown in immune regulation, resulting in the expansion of autoreactive CD4? and CD8? T cells and destruction of the insulin-producing b-cells [1]. Animal models of autoimmune diabetes have indicated that IFN-csecreting Th1 cells are key players in the destruction of b cells as activators of cytotoxic CD8? cells. More recently, Th17 immunity has been demonstrated in the development of autoimmune diabetes in NOD mice [2, 3] and humans [4]. Th17 cells are inflammatory CD4? T cells that produce IL-17 [5]. IL-17 has detrimental effects on human islet cells via inflammatory responses [4]. It also mediates significant and reproducible enhancement of IL-1b/IFN-cinduced and TNF-a/IFN-c-induced apoptosis in human islets [6]. Circulating IL-17(?) b-cell-specific autoreactive CD4? T cells are a feature of type 1 diabetes diagnosis [6, 7]. Th22 cells differ from Th17 and Th1 cells in their differentiation and function as they express low or undetectable Th17 and the Th1-associated transcription factors RORct and T-bet. Notably, the Aryl hydrocarbon receptor (AHR) has been shown to b
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