Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Milan, Italy.
Laboratory of Mucosal Immunology and Microbiota, Humanitas Clinical and Research Center, Milan, Italy.
Front Immunol. 2020 Mar 31;11:509. doi: 10.3389/fimmu.2020.00509. eCollection 2020.
The evolution of the full range of functions of regulatory T cells (Treg) coincides with the evolution of mammalian pregnancy. Accordingly, Treg function has been shown to be crucial for maternal-fetal tolerance and implantation. As reproduction is a key point of selective pressure, mammalian pregnancy may represent an evolutionary driver for the development of Treg. Yet beyond the chronological boundaries of mammalian pregnancy, several key physiological and pathological events are being gradually uncovered as involving the immunomodulating functions of Treg cells. These include autoimmunity, age-related inflammation in males and in post-menopausal females, but also oncological and cardiovascular diseases. The latter two sets of diseases collectively compose the main causes of mortality world-wide. Emerging data point to Treg-modulable effects in these diseases, in a departure from the relatively narrower perceived role of Treg as master regulators of autoimmunity. Yet recent evidence also suggests that changes in intestinal microbiota can affect the above pathological conditions. This is likely due to the finding that, whilst the presence and maintenance of intestinal microbiota requires active immune tolerance, mediated by Treg, the existence of microbiota profoundly affects the polarization, stability, and balance of pro- and anti-inflammatory T cell populations, including Treg and induced Treg cells. The study of these "novel," but possibly highly relevant from an ontogenesis perspective, facets of Treg function may hold great potential for our understanding of the mechanisms underlying human disease.
调节性 T 细胞（Treg）的全功能进化与哺乳动物妊娠的进化相吻合。因此，Treg 功能对于母胎耐受和着床至关重要。由于生殖是选择压力的关键点，哺乳动物妊娠可能代表了 Treg 发展的进化驱动力。然而，除了哺乳动物妊娠的时间界限之外，几个关键的生理和病理事件逐渐被揭示与 Treg 细胞的免疫调节功能有关。这些包括自身免疫、男性和绝经后女性的年龄相关炎症，以及肿瘤和心血管疾病。后两组疾病共同构成了全球死亡的主要原因。新出现的数据表明，Treg 可调节这些疾病的发生，这与人们普遍认为 Treg 是自身免疫的主要调节者的观点有所不同。然而，最近的证据也表明，肠道微生物群的变化可能会影响上述病理状况。这可能是由于发现，虽然肠道微生物群的存在和维持需要由 Treg 介导的主动免疫耐受，但微生物群的存在深刻地影响了促炎和抗炎 T 细胞群，包括 Treg 和诱导的 Treg 细胞的极化、稳定性和平衡。从个体发生学的角度来看，研究这些“新出现的”但可能具有高度相关性的 Treg 功能方面，可能为我们理解人类疾病的机制提供很大的潜力。
