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Bcl6 modulates innate immunity by controlling macrophage activity and plays critical role in experimental autoimmune encephalomyelitis.
European Journal of Immunology ( IF 5.4 ) Pub Date : 2020-02-25 , DOI: 10.1002/eji.201948299
Qing Li 1 , Lei Zhou 1 , Ling Wang 1 , Shiqiang Li 1 , Guiliang Xu 1 , Haijuan Gu 1 , Dali Li 1 , Mingyao Liu 1 , Lei Fang 2 , Zhengyi Wang 2 , Shuhua Han 2 , Biao Zheng 1, 2
Affiliation  

The B-cell CLL/lymphoma 6 (Bcl6) oncogenic repressor is a master regulator of humoral immunity and B-cell lymphomagenesis. Although much research has focused on its regulation and function of GC B cells and T cells, the role of Bcl6 in regulating the functions of innate immunity is not well defined. Here, we demonstrated that EAE is exacerbated in LysM Cre+/ - Bcl6fl/fl mice. Although other cells such as neutrophils might be involved in this conditional mutant mouse model, we found that the disease pathology is mainly associated with a biased M1 macrophage activity and an enhanced encephalitogenic CD4+ Th17 cell response. In addition, LPS-induced sepsis mice exhibited an enhanced M1 and inhibited M2 response, further confirming that Bcl6 has an important role in regulating macrophage polarization. Mechanistically, Bcl6 interacts with IκBζ and interferes its binding to the interleukin-6 (Il-6) promoter in macrophages, leading to a suppressed transcription of Il-6. These findings have demonstrated that Bcl6 exerts its regulatory function mainly by repressing Il-6 expression in macrophages. Thus, our study presents a novel role for Bcl6 in regulating immune response and inflammation. Interaction between Bcl6 and IκBζ in macrophages may provide a potential therapeutic target for autoimmune inflammatory disease.

中文翻译:

Bcl6通过控制巨噬细胞活性来调节先天免疫,并在实验性自身免疫性脑脊髓炎中起关键作用。

B细胞CLL /淋巴瘤6(Bcl6)致癌阻遏物是体液免疫和B细胞淋巴瘤发生的主要调节剂。尽管许多研究集中在其对GC B细胞和T细胞的调节和功能上,但Bcl6在调节先天免疫功能中的作用尚不清楚。在这里,我们证明了EAE在LysM Cre +/- Bcl6fl / fl小鼠中恶化。尽管其他细胞(例如嗜中性粒细胞)可能参与此条件突变小鼠模型,但我们发现该疾病病理学主要与M1巨噬细胞活性偏倚和致脑性CD4 + Th17细胞反应增强有关。此外,LPS诱导的败血症小鼠表现出增强的M1和抑制的M2反应,进一步证实Bcl6在调节巨噬细胞极化中起重要作用。机械上,Bcl6与IκBζ相互作用并干扰其与巨噬细胞中白介素6(Il-6)启动子的结合,从而导致Il-6的转录受到抑制。这些发现表明,Bcl6主要通过抑制巨噬细胞中的Il-6表达来发挥其调节功能。因此,我们的研究提出了Bcl6在调节免疫反应和炎症中的新作用。巨噬细胞中Bcl6与IκBζ之间的相互作用可能为自身免疫性炎性疾病提供潜在的治疗靶点。
更新日期:2020-02-25
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