Abstract:Abstract: The germinal center (GC) formation and autoantibody production are found in various autoimmune diseases. T follicular helper (Tfh) cells and germinal center B (GC B) cells are indispensable during GC formation. B cell lymphoma 6 (BCL6) is a main transcription factor of Tfh cells and GC B cells. Loss of BCL6 in these two cell types results in abrogation of the GC reaction. Herein, small molecule compound WK429 targeting BCL6BTB domain was discovered by homogeneous time-resolved fluorescence (HTRF) screening system. In vitro, WK429 inhibited the production of inflammatory factors IL-6 and TNF-α in peripheral blood mononuclear cells (PBMCs) and Raw264.7 cells, and also diminished the mRNA abundance of chemokine genes (CCL2 and CCL7) in Raw264.7 cells. WK429 not only restrained the formation of Tfh cells, GC B cells and plasma cells, but also depressed the division of plasma cells. In vivo, WK429 similarly restrained the formation of Tfh cells, GC B cells and plasma cells, and dramatically decreased the production of IgG antibodies. Collectively, this study demonstrated that WK429 could inhibit inflammation and reduce humoral immune responses, which may provide new strategies for the prevention or treatment of autoimmune diseases with excessive humoral immune responses.
引用本文:
胡 盼, 邢雅婧, 彭世鸿, 谢玖清, 郭伟凯, 谢佳伊, 刘明耀, 易正芳. 小分子化合物WK429抑制炎症和降低体液免疫反应的研究[J]. 生命科学研究, 2020, 24(5): 382-395.
HU Pan, XING Ya-jing, PENG Shi-hong, XIE Jiu-qing, GUO Wei-kai, XIE Jia-yi, LIU Ming-yao, YI Zheng-fang. Inhibition of Inflammation and Reduction of Humoral Immune Responses by Small Molecule Compound WK429. Life Science Research, 2020, 24(5): 382-395.