BACH2 regulates the function of human CD4+CD45RA-Foxp3l° cytokine-secreting T cells and promotes B-cell response in systemic lupus erythematosus
BACH2 regulates the function of human CD4+CD45RA-Foxp3l° cytokine-secreting T cells and promotes B-cell response in systemic lupus erythematosus
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BACH2 调节人 CD4( ) CD45RA(-) Foxp3(l) ° 细胞因子分泌 T 细胞的功能，并促进系统性红斑狼疮中的 B 细胞反应。
DOI：
10.1002/eji.201948320
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发表时间：
2019-12-19
影响因子：
5.4
通讯作者：
Shen, Lisong
中科院分区：
文献类型：
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作者：
Zheng, Yingxia;Lu, Yiwen;Shen, Lisong
虽然已有报道系统性红斑狼疮（SLE）患者中分泌CD 4（+）CD 45 RA（-）Foxp 3（1）度亮氨酸的T细胞（Fr.III细胞）增加，但其功能及其对B细胞应答的影响尚不清楚。在这里，我们剖析BACH 2如何调节Fr.III细胞的功能，并促进活动性SLE患者的B细胞反应。我们测量了细胞因子和BACH 2表达，发现在共培养系统中，来自SLE患者的Fr.III细胞产生更多的炎性细胞因子，并且比对照更能够促进B细胞增殖、IgG、伊加和TNF-α的产生。Fr.III细胞高表达ICOS和CD 154，低表达Tfr和BACH 2，BACH 2表达与SLE疾病活动指数呈负相关。BACH 2在Fr.III细胞中过表达，降低细胞因子表达和降低B细胞反应。此外，我们确定了SLE Fr.III细胞中BACH 2基因座处H3 K27 ac水平结合的降低，并且SLE血清刺激降低了BACH 2基因座处的H3 K27 ac结合，这可以使用阿司他汀A（TSA）恢复。总之，BACH 2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。以BACH 2为靶点可能成为SLE免疫干预治疗的新途径。
Although CD4(+)CD45RA(-)Foxp3(l)degrees 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-alpha 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.