AUTHOR=Yao Qiu-ming , Li Ling , Song Zhen-Yu , Wang Bin , Qin Qiu , An Xiao-fei , Zhang Jin-an 

TITLE=Elevated Interleukin-36α And CD4+IL-36α+T Cells Are Involved in the Pathogenesis of Graves' Disease

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00591

DOI=10.3389/fendo.2018.00591

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold> IL-36α is involved in the pathogenesis of a variety of autoimmune diseases, but the relationship between IL-36α and Graves' disease (GD) has rarely investigated. In the present study, we aimed to explore the expression of IL-36α and elucidate the potential role of IL-36α in GD.</p><p><bold>Methods:</bold> The expression of IL-36α mRNA in peripheral blood mononuclear cells (PBMCs) from 32 newly diagnosed GD patients, 15 refractory GD patients and 30 normal controls (NC) was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The level of IL-36α in serum from 46 newly diagnosed GD patients, 10 refractory GD patients and 24 NC was measured using enzyme linked immunosorbent assay (ELISA). The percentage of CD4<sup>+</sup>IL-36α<sup>+</sup>T cells was detected by flow cytometry. PBMCs from newly diagnosed GD patients and NC group were cultured in the presence or absence of recombinant human IL-36α, and the expression levels of IFN-γ, TNF-α, IL-6, and IL-17A in culture supernatant were detected by cytokine array.</p><p><bold>Results:</bold> The expression of IL-36α mRNA in newly diagnosed GD patients was significantly higher than that in NC group (<italic>P</italic> = 0.019). IL-36α mRNA expression was positively associated with thyrotropin receptor antibody (TRAb) (<italic>P</italic> = 0.004, <italic>r</italic> = 0.498) in newly diagnosed GD patients. The level of IL-36α in serum from newly diagnosed GD patients was significantly higher than that in refractory GD patients and NC group (<italic>P</italic> = 0.01; <italic>P</italic> = 0.007). The percentage of CD4<sup>+</sup>IL-36α<sup>+</sup>T cells in newly diagnosed GD patients was significantly higher than that in NC group (<italic>P</italic> = 0.030). In GD group, recombinant human IL-36α stimulation resulted in the increase of INF-γ, TNF-α, IL-6 and IL-17A (<italic>P</italic> = 0.015; <italic>P</italic> = 0.016; <italic>P</italic> = 0.039; <italic>P</italic> = 0.017).</p><p><bold>Conclusion:</bold> IL-36α and CD4<sup>+</sup>IL-36α<sup>+</sup>T cells may be involved in the pathogenesis of GD by promoting the production of Th1, Th2, and Th17 cytokines.</p>