IFN-b acts on monocytes to ameliorate CNS autoimmunity by inhibiting proinflammatory cross-talk between monocytes and Th cells. IFN-b acts on monocytes to ameliorate CNS autoimmunity by inhibiting proinflammatory cross-talk between monocytes and Th cells

Multiple sclerosis (MS) has been treated with IFN-b for three decades, but the mechanisms underlying its beneficial effects are not well understood. Our study elucidates, in a mouse model of MS, a potential mechanism whereby IFN-b inhibits cooperation between monocytes and T cells, two key immune cell types in MS. We found that IFN-b acts on monocytes to induce secretion of anti-inflammatory molecules, IL-10 and TGF-b, which act on T cells to suppress their production of pro-inflammatory molecules, GM-CSF, TNF, and FASL. Given that these T cell molecules induce proinflammatory features of monocytes, such as IL-1b production, we concluded that IFN-b therapy suppresses cooperation between monocytes and T cells, which otherwise reciprocally amplifies their harmful roles in MS. Overall design: WT/IFNAR1-/- mix bone marrow chimera mice were generated, immunized for EAE induction, and treated with IFN-b daily. WT and IFNAR1-/- monocytes were isolated and their transcriptome were analyzed by RNA sequencing

多发性硬化症（Multiple Sclerosis, MS）的临床治疗已使用干扰素β（Interferon-β, IFN-β）长达三十年，但其发挥有益治疗作用的分子机制仍未得到充分阐明。本研究在MS小鼠模型中，阐明了干扰素β抑制单核细胞与T细胞协同作用的潜在机制——二者均为MS发病过程中的关键免疫细胞类型。研究发现，干扰素β可直接作用于单核细胞，诱导其分泌抗炎分子白细胞介素10（Interleukin-10, IL-10）与转化生长因子-β（Transforming Growth Factor-β, TGF-β）；上述细胞因子可进一步作用于T细胞，抑制其促炎相关分子粒细胞-巨噬细胞集落刺激因子（Granulocyte-Macrophage Colony-Stimulating Factor, GM-CSF）、肿瘤坏死因子（Tumor Necrosis Factor, TNF）及FAS配体（FAS Ligand, FASL）的产生。鉴于此类T细胞来源的促炎分子可诱导单核细胞产生白细胞介素1β（Interleukin-1β, IL-1β）等促炎表型，本研究最终确认：干扰素β疗法可有效抑制单核细胞与T细胞的协同互作；若缺乏该调控通路，二者将相互促进并放大其在MS中的有害致病作用。整体实验设计：构建野生型（Wild Type, WT）与干扰素α/β受体1敲除（Interferon α/β Receptor 1 knockout, IFNAR1-/-）混合骨髓嵌合小鼠，通过主动免疫诱导构建实验性自身免疫性脑脊髓炎（Experimental Autoimmune Encephalomyelitis, EAE）模型，随后每日给予干扰素β处理。分离WT及IFNAR1-/-单核细胞，通过RNA测序（RNA Sequencing）对其转录组进行分析。