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 per se 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.

中文翻译：

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超越自身免疫的调节性T细胞：从怀孕到癌症和心血管疾病。

调节性T细胞（Treg）的全部功能的演变与哺乳动物妊娠的发展相吻合。因此，已经表明Treg功能对于母胎耐受性和植入至关重要。由于繁殖是选择压力的关键，哺乳动物妊娠可能代表了Treg的进化驱动力。然而，超越哺乳动物妊娠的时间界限，由于涉及Treg细胞的免疫调节功能，一些关键的生理和病理事件正在逐渐被发现。这些疾病包括男性和绝经后女性的自身免疫，与年龄相关的炎症，以及肿瘤和心血管疾病。后两种疾病共同构成了全世界死亡的主要原因。新兴数据表明这些疾病中Treg可调节的作用，与Treg作为自身免疫的主要调节剂的相对狭窄的作用背道而驰。然而，最近的证据还表明，肠道菌群的变化会影响上述病理状况。这可能是由于以下发现：虽然肠道微生物群的存在和维持需要Treg介导的主动免疫耐受，但微生物群本身的存在本身会深刻影响促炎性T细胞和消炎性T细胞的极化，稳定性以及平衡人群，包括Treg和诱导的Treg细胞。对这些“新颖”的研究，但从本体论的角度看可能非常相关，Treg功能的各个方面可能为我们理解人类疾病的潜在机制具有巨大的潜力。不同于Treg作为自身免疫的主要调节剂的相对狭窄的作用。然而，最近的证据还表明，肠道菌群的变化会影响上述病理状况。这可能是由于以下发现：虽然肠道微生物群的存在和维持需要Treg介导的主动免疫耐受，但微生物群本身的存在本身会深刻影响促炎性T细胞和消炎性T细胞的极化，稳定性以及平衡人群，包括Treg和诱导的Treg细胞。对这些“新颖”的研究，但从本体论的角度看可能非常相关，Treg功能的各个方面可能为我们理解人类疾病的潜在机制具有巨大的潜力。不同于Treg作为自身免疫的主要调节剂的相对狭窄的作用。然而，最近的证据还表明，肠道菌群的变化会影响上述病理状况。这可能是由于以下发现：虽然肠道微生物群的存在和维持需要Treg介导的主动免疫耐受，但微生物群本身的存在本身会深刻影响促炎性T细胞和消炎性T细胞的极化，稳定性以及平衡人群，包括Treg和诱导的Treg细胞。对这些“新颖”的研究，但从本体论的角度看可能非常相关，Treg功能的各个方面可能为我们理解人类疾病的潜在机制具有巨大的潜力。