BACH2 regulates the function of human CD4+ CD45RA- Foxp3l ° cytokine-secreting T cells and promotes B-cell response in systemic lupus erythematosus.,European Journal of Immunology

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BACH2 regulates the function of human CD4+ CD45RA- Foxp3l ° cytokine-secreting T cells and promotes B-cell response in systemic lupus erythematosus.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2019-12-19 , DOI: 10.1002/eji.201948320
Yingxia Zheng _{1,

2} , Yiwen Lu ₁ , Xinfang Huang ₃ , Li Han ₁ , Zheyi Chen ₁ , Bingqian Zhou ₁ , Yanhui Ma ₁ , Guohua Xie ₁ , Junyao Yang ₁ , Bingxian Bian ₁ , Li Li ₁ , Hong Nie ₄ , Xiujun Pan ₁ , Lisong Shen ₁

Affiliation

Although CD4+ CD45RA- Foxp3l ° cytokine-secreting T cells (Fr.III cells) have been reported to be increased in systemic lupus erythematosus (SLE), their function and effects on response of B cells are still unclear. Here, we dissect how BACH2 regulates Fr.III cells function and promotes B-cell response in active SLE patients. We measured cytokines and BACH2 expression, and found that Fr.III cells from SLE patients produce much more inflammatory cytokines and were more able to promote B- cell proliferation, IgG, IgA, and TNF-α production than controls in a co-culture system. Fr.III cells expressed high levels of ICOS and CD154, but a low level of Tfr and BACH2, BACH2 expression was negatively correlated with SLE Disease Activity Index. Overexpressed of BACH2 in Fr.III cells, decreased cytokines expression and reduced B-cell response. Furthermore, we identified a reduction of H3K27ac level binding at the BACH2 locus in the SLE Fr.III cells and SLE serum stimulation decreased H3K27ac binding at the BACH2 locus, which could be restored using trichostatin A (TSA). In conclusion, BACH2 was associated with SLE disease activity, regulated the function of Fr.III cells, and promoted B-cells response. Targeting BACH2 may be a new immune intervention therapy of SLE.

中文翻译：

BACH2调节人CD4 + CD45RA- Foxp31l细胞因子分泌性T细胞的功能，并促进系统性红斑狼疮的B细胞反应。

虽然据报道CD4 + CD45RA- Foxp31l细胞因子分泌性T细胞（Fr.III细胞）在系统性红斑狼疮（SLE）中增加，但其功能和对B细胞反应的影响尚不清楚。在这里，我们分析了活跃的SLE患者中BACH2如何调节Fr.III细胞功能并促进B细胞反应。我们测量了细胞因子和BACH2表达，发现与共培养系统中的对照相比，SLE患者的Fr.III细胞产生了更多的炎性细胞因子，并且能够促进B细胞增殖，IgG，IgA和TNF-α的产生。。Fr.III细胞表达高水平的ICOS和CD154，但低水平的Tfr和BACH2，BACH2表达与SLE疾病活动指数呈负相关。在Fr.III细胞中过表达BACH2，降低了细胞因子的表达，并降低了B细胞的反应。此外，我们发现SLE Fr.III细胞中BACH2位点的H3K27ac水平结合减少，SLE血清刺激降低了BACH2位点的H3K27ac结合，这可以用曲古抑菌素A（TSA）恢复。总之，BACH2与SLE疾病活动相关，调节Fr.III细胞的功能，并促进B细胞反应。靶向BACH2可能是SLE的一种新的免疫干预疗法。

更新日期：2019-12-19

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