The TGF-β/miR-31/CEACAM1-S axis inhibits CD4 CD25 Treg differentiation in systemic lupus erythematosus.
发布时间：2021-06-02
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影响因子：3.745
发表刊物：Immunol Cell Biol
关键字：CEACAM1-S; NF-κB; Treg; miR-31; systemic lupus erythematous.
摘要：Defects causing concomitant loss of CD25 expression in regulatory T cells (Tregs) have been identified in systemic lupus erythematosus (SLE). However, the cause of this deficiency is not fully understood. Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), an immune co-receptor, contributes to general T-cell function and activation. Our previous study revealed that CEACAM1 expression was upregulated in peripheral blood mononuclear cells (PBMCs) from patients with SLE. However, its role remains unclear. Herein, we confirmed CEACAM1, especially CEACAM1-S, was upregulated in PBMCs from patients with SLE. CEACAM1-S over-expression inhibits CD4+ CD25+ Treg differentiation, whereas knockdown of CEACAM1 had the opposite effect in vitro. CEACAM1-S is the target of miR-31. MiR-31 mimic inhibits CEACAM1 expression and enhances CD4+ CD25+ Treg differentiation, which was reversed by CEACAM1-S over-expression. Moreover, the circulating TGF-β level was upregulated in SLE patients and TGF-β reduced miR-31 expression via enhancing NF-κB activity. Importantly, CEACAM1 and TGF-β mRNA levels were downregulated, while the miR-31 level and the abundance of CD4+ CD25+ Tregs were increased in inactive patients compared with that in patients with active SLE. In addition, CEACAM1-S expression was positively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, while CD4+ CD25+ Treg abundance and miR-31 level were negatively correlated with the SLEDAI score. In conclusion, reduced activity of miR-31 by TGF-β, via the inhibition of NF-ᴋB, acted to inhibit the differentiation of CD4+ CD25+ Tregs by directly targeting CEACAM1-S and to promote autoimmunity.
合写作者：Yang Yang,Tao Li,Yunfei Xu,Wenqin Zhang,Muyuan Li,Yizhi Xiao,Jie Hu,Ke Liu,Quanzhen Li,Ming Gui,Xiaoxia Zuo
第一作者：Yanjuan Liu,Caiyan Li
论文类型：基础研究
通讯作者：Yisha Li,Huali Zhang（通讯作者）
学科门类：医学
一级学科：基础医学
期号：2021 Mar 2.doi: 10.1111/imcb.12449.
是否译文：否
发表时间：2021-03-02
收录刊物：SCI