Bcl6 modulates innate immunity by controlling macrophage activity and plays critical role in experimental autoimmune encephalomyelitis. Issue 4 (25th February 2020)

• Record Type: Journal Article
• Authors: Li, Qing; Zhou, Lei; Wang, Ling; Li, Shiqiang; Xu, Guiliang; Gu, Haijuan; Li, Dali; Liu, Mingyao; Fang, Lei; Wang, Zhengyi; Han, Shuhua; Zheng, Biao
• Is Part Of: European journal of immunology. Volume 50:Issue 4(2020)
• Page Start: 525
• Page End: 536
• Publication Date: 2020-02-25
• Subjects: Bcl6 -- EAE -- IL‐6 -- Macrophages -- Th17; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201948299
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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 +/ − Bcl6 fl/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. Abstract : By analysis of several macrophage subsets, we have demonstrated that Bcl6 regulates macrophage IL‐6 production, which plays important role in EAE. This crosstalk between Th17 cells and macrophage mediated by Bcl6 provides insight into the mechanisms that control the development and progression of autoimmune disease.