小柯机器人

美国明尼苏达大学医学院免疫学中心Marc K. Jenkins研究组发现，食物的免疫耐受是由多层CD4+ T细胞功能障碍介导的。该项研究成果发表在2022年7月6日出版的《自然》上。

他们使用敏感细胞富集方法来解决免疫系统耐受矛盾难题，以表明多克隆 CD4+ T 细胞对食物肽（包括来自麦醇溶蛋白的天然肽）作出反应，由于调节作用，在肠-肝轴的次级淋巴器官中增殖较弱T细胞。一些食物特异性 T 细胞随后分化为 T 滤泡辅助细胞，从而促进了微弱的抗体反应。然而，扩增群体中的大多数细胞缺乏典型的 T 辅助细胞谱系标记，并分为五个亚群，由先天样或 T 滤泡辅助细胞样无能细胞主导，形成炎性 T 辅助细胞 1 细胞的能力有限。最终，许多 T 辅助细胞谱系阴性细胞通过白介素 2 依赖性机制自身成为调节性 T 细胞。

他们的研究结果表明，接触食物抗原会导致同源 CD4+ 先天T 细胞形成一组复杂的非典型低反应性 T 辅助细胞亚群，这些亚群缺乏引起肠道病理学所需的炎症功能，但有可能产生抑制它的调节性 T 细胞.

据介绍，胃肠道健康取决于适应性免疫系统对食物中外来蛋白质的耐受性。这种耐受性是矛盾的，因为免疫系统通常会通过产生炎症来攻击外来物质。

附：英文原文

Title: Immune tolerance of food is mediated by layers of CD4+ T cell dysfunction

Author: Hong, Sung-Wook, Krueger, Peter D., Osum, Kevin C., Dileepan, Thamotharampillai, Herman, Adam, Mueller, Daniel L., Jenkins, Marc K.

Issue&Volume: 2022-07-06

Abstract: Gastrointestinal health depends on the adaptive immune system tolerating the foreign proteins in food1,2. This tolerance is paradoxical because the immune system normally attacks foreign substances by generating inflammation. Here we addressed this conundrum by using a sensitive cell enrichment method to show that polyclonal CD4+ T cells responded to food peptides, including a natural one from gliadin, by proliferating weakly in secondary lymphoid organs of the gut–liver axis owing to the action of regulatory T cells. A few food-specific T cells then differentiated into T follicular helper cells that promoted a weak antibody response. Most cells in the expanded population, however, lacked canonical T helper lineage markers and fell into five subsets dominated by naive-like or T follicular helper-like anergic cells with limited capacity to form inflammatory T helper 1 cells. Eventually, many of the T helper lineage-negative cells became regulatory T cells themselves through an interleukin-2-dependent mechanism. Our results indicate that exposure to food antigens causes cognate CD4+ naive T cells to form a complex set of noncanonical hyporesponsive T helper cell subsets that lack the inflammatory functions needed to cause gut pathology and yet have the potential to produce regulatory T cells that may suppress it.

DOI: 10.1038/s41586-022-04916-6

Source: https://www.nature.com/articles/s41586-022-04916-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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