Identify The Function And Mechanism Of Macrophage BCL6 In Autoimmune Disease EAE

As one of the anti-apoptosis family members,oncogenic BCL6 plays an important re-pressor functional role in humoral immunity and B cell lymphomagenesis.Whereas many researches have focused on its regulation and function in follicular T-and germi-nal center B-cells,the role of BCL6 in regulating innate immune system and autoim-mune is not well clear.Here we demonstrated that macrophage BCL6 deficient mice(LysM ^cre+/-BCL6^f/f)showed significantly upregulated Th17 differentiation and exacer-bated neuro-inflammation in experimental autoimmune encephalomyelitis model?EAE model?.At the cellular level,macrophage BCL6 deficient mice showed an elevated IL-6 pro-duction and developed an increased encephalitogenic CD4⁺Th17 cell response which is the result of enhanced“crosstalk”between macrophages and CD4⁺T cells.For mechanism,we identified that BCL6 regulates IL-6 production by interacting with the transcription factor,I?B?.The interaction between BCL6 and I?B?interfered the binding activity of I?B?to the Il-6 promotor,leading to a suppressed transcription of Il-6.So,we identify a novel role of BCL6 in regulating immunity and inflammation.Our study figures out an important role of macrophage BCL6 in controlling the production of IL-6,which promotes the“crosstalk”between macrophages and T cells,and then resulting a regulation of autoimmune disease and Th17 differentiation.Interaction be-tween BCL6 and I?B?in macrophages may provide a potential therapeutic target for clinical autoimmune disease.