Neuropilin-1 (NRP1) expression distinguishes self-reactive helper T cells in systemic autoimmune disease.
Neuropilin-1 (NRP1) expression distinguishes self-reactive helper T cells in systemic autoimmune disease.
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DOI：
10.15252/emmm.202215864
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发表时间：
2022-10-10
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
对自身抗原有反应的病原性辅助性T细胞（Th细胞）与有益的Th细胞不易区分。这些细胞可以产生系统性自身免疫性疾病，以响应广泛表达的自身抗原。在这项研究中，我们已经确定了神经纤毛蛋白-1（NRP 1）作为自身反应性Th细胞的细胞表面标志物。NRP 1 + Th细胞在正常小鼠的非调节性T细胞亚群中不存在，但在系统性自身免疫性疾病模型中出现，并与疾病症状密切相关。NRP 1 + Th细胞在Nr 4a 2 cKO小鼠中大大减少，其自身反应性应答降低，但对外源性抗原显示正常应答。NRP 1 + Th细胞的转移足以引发或加速全身性自身免疫性疾病，靶向表达NRP 1的Th细胞治疗性改善了BXSB-Yaa小鼠的SLE样自身免疫性症状。SLE患者外周血NRP 1 + Th细胞明显增加。我们的数据表明，自身反应性Th细胞可以在Th细胞池中进行表型区分。这些发现提供了一种新的方法来识别自身反应性Th细胞，并靶向它们来治疗系统性自身免疫性疾病。在系统性自身免疫性疾病中，自身反应性Th细胞支持B细胞产生针对一系列自身抗原的致病性自身抗体。发现致病性自身反应性Th细胞的标记物允许靶向这些反应以治疗疾病，而不管抗原如何。
Pathogenic T helper cells (Th cells) that respond to self‐antigen cannot be easily distinguished from beneficial Th cells. These cells can generate systemic autoimmune disease in response to widely expressed self‐antigens. In this study, we have identified neuropilin‐1 (NRP1) as a cell surface marker of self‐reactive Th cells. NRP1+ Th cells, absent in non‐regulatory T cell subsets in normal mice, appeared in models of systemic autoimmune disease and strongly correlated with disease symptoms. NRP1+ Th cells were greatly reduced in Nr4a2 cKO mice, which have reduced self‐reactive responses but showed normal responses against exogenous antigens. Transfer of NRP1+ Th cells was sufficient to initiate or accelerate systemic autoimmune disease, and targeting NRP1‐expressing Th cells therapeutically ameliorated SLE‐like autoimmune symptoms in BXSB‐Yaa mice. Peripheral NRP1+ Th cells were significantly increased in human SLE patients. Our data suggest that self‐reactive Th cells can be phenotypically distinguished within the Th cell pool. These findings offer a novel approach to identify self‐reactive Th cells and target them to treat systemic autoimmune disease. In systemic autoimmune disease, self‐reactive Th cells support B cells to make pathogenic autoantibodies against a range of self‐antigens. Finding a marker of pathogenic self‐reactive Th cells allows targeting of these responses to treat disease regardless of antigen.
影响因子：
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作者：
Kim JY;Han JH;Park G;Seo YW;Yun CW;Lee BC;Bae J;Moon AR;Kim TH
通讯作者：
Kim TH
影响因子：
3.7
作者：
Durinovic-Belló I;Gersuk VH;Ni C;Wu R;Thorpe J;Jospe N;Sanda S;Greenbaum CJ;Nepom GT
通讯作者：
Nepom GT