Chen Swey-Shen, Sun Liang-Wu, Brickner Howard, Sun Pei-Qing
Department of Immunology, The Institute of Genetics, San Diego, CA, USA; Department of Allergy, Inflammation and Vaccinology, IGE Therapeutics, Inc., San Diego, CA, USA; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA.
Department of Immunology, The Institute of Genetics, San Diego, CA, USA; Department of Allergy, Inflammation and Vaccinology, IGE Therapeutics, Inc., San Diego, CA, USA.
Cell Immunol. 2015 Mar;294(1):44-53. doi: 10.1016/j.cellimm.2015.01.017. Epub 2015 Feb 7.
Galectin-3 (Gal-3), a β-galactoside-binding lectin, serves as a pattern-recognition receptor (PRR) of dendritic cells (DCs) in regulating proinflammatory cytokine production. Galectin-3 (Gal-3) siRNA downregulates expression of IL-6, IL-1β and IL-23 p19, while upregulates IL-10 and IL-12 p35 in TLR/NLR stimulated human MoDCs. Furthermore, Gal-3 siRNA-treated MoDCs enhanced IFN-γ production in SEB-stimulated CD45RO CD4 T-cells, but attenuated IL-17A and IL-5 production by CD4 T-cells. Addition of neutralizing antibodies against Gal-3, or recombinant Gal-3 did not differentially modulate IL-23 p19 versus IL-12 p35. The data indicate that intracellular Gal-3 acts as cytokine hub of human DCs in responding to innate immunity signals. Gal-3 downregulation reprograms proinflammatory cytokine production by MoDCs that inhibit Th2/Th17 development.
半乳糖凝集素-3（Gal-3）是一种β-半乳糖苷结合凝集素，作为树突状细胞（DCs）的模式识别受体（PRR），在调节促炎细胞因子产生方面发挥作用。在Toll样受体/核苷酸结合寡聚化结构域样受体（TLR/NLR）刺激的人单核细胞来源的树突状细胞（MoDCs）中，Galectin-3（Gal-3）小干扰RNA（siRNA）下调白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和白细胞介素-23 p19的表达，同时上调IL-10和IL-12 p35的表达。此外，经Gal-3 siRNA处理的MoDCs增强了在葡萄球菌肠毒素B（SEB）刺激的CD45RO CD4 T细胞中干扰素-γ（IFN-γ）的产生，但减弱了CD4 T细胞产生白细胞介素-17A（IL-17A）和白细胞介素-5（IL-5）的能力。添加抗Gal-3中和抗体或重组Gal-3对IL-23 p19和IL-12 p35的调节没有差异。这些数据表明，细胞内Gal-3在人类DCs响应先天免疫信号时充当细胞因子枢纽。Gal-3下调可重新编程MoDCs的促炎细胞因子产生，从而抑制Th2/Th17的发育。
