Neuropilin-1 Identifies a New Subpopulation of TGF-β-Induced Foxp3(+) Regulatory T Cells With Potent Suppressive Function and Enhanced Stability During Inflammation.
Neuropilin-1 Identifies a New Subpopulation of TGF-β-Induced Foxp3(+) Regulatory T Cells With Potent Suppressive Function and Enhanced Stability During Inflammation.
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DOI：
10.3389/fimmu.2022.900139
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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CD 4 + Foxp 3+调节性T细胞（TCRs）在预防自身免疫和炎症中起着至关重要的作用。有胸腺内天然产生的（tTreg）、外周胸腺外产生的（pTreg）和体外诱导培养的（iTreg），具有不同的抑制性、稳定性和可塑性特征。关于神经纤毛蛋白-1（Nrp-1）作为tTreg标记物的已发表数据丰富，但关于iTreg的数据很少。Nrp-1作为tTreg标志物的保真度及其在iTreg中的作用仍有待探索。这项研究发现，Nrp-1在完整小鼠的中枢和外周淋巴器官以及iTreg中由Foxp 3 + CD 4 +T细胞亚群表达。将Nrp-1+iTreg和Nrp-1-iTreg过继转移到T细胞介导的结肠炎模型中，以确定它们抑制炎症的能力。通过RNA测序分析Nrp-1+和Nrp-1-iTreg之间的基因表达差异。我们证明，与体内和体外的Nrp-1-对应物相比，iTreg的Nrp-1+子集表现出增强的抑制功能和稳定性，部分取决于IL-10。我们发现Nrp-1不是tTreg的唯一标志物，然而，它是鉴定具有增强的抑制功能的iTreg的新子集的生物标志物，暗示Nrp-1+iTreg细胞治疗自身免疫性和炎性疾病的潜力。
CD4+Foxp3+ regulatory T cells (Tregs) play a crucial role in preventing autoimmunity and inflammation. There are naturally-derived in the thymus (tTreg), generated extrathymically in the periphery (pTreg), and induced in vitro culture (iTreg) with different characteristics of suppressiveness, stability, and plasticity. There is an abundance of published data on neuropilin-1 (Nrp-1) as a tTreg marker, but little data exist on iTreg. The fidelity of Nrp-1 as a tTreg marker and its role in iTreg remains to be explored. This study found that Nrp-1 was expressed by a subset of Foxp3+CD4+T cells in the central and peripheral lymphoid organs in intact mice, as well as in iTreg. Nrp-1+iTreg and Nrp-1-iTreg were adoptively transferred into a T cell-mediated colitis model to determine their ability to suppress inflammation. Differences in gene expression between Nrp-1+ and Nrp-1-iTreg were analyzed by RNA sequencing. We demonstrated that the Nrp-1+ subset of the iTreg exhibited enhanced suppressive function and stability compared to the Nrp-1- counterpart both in vivo and in vitro, partly depending on IL-10. We found that Nrp-1 is not an exclusive marker of tTreg, however, it is a biomarker identifying a new subset of iTreg with enhanced suppressive function, implicating a potential for Nrp-1+iTreg cell therapy for autoimmune and inflammatory diseases.