小柯机器人

美国芝加哥大学Bana Jabri和Ankit Malik共同合作，近期取得重要工作进展。他们研究发现，上皮IFNγ信号传导和区隔抗原呈递协调肠道免疫。相关研究成果2023年11月22日在线发表于《自然》杂志上。

据介绍，所有的有核细胞都表达主要组织相容性复合体I和干扰素-γ（IFNγ）受体，但目前人们尚未探索上皮细胞特异性的IFNγ信号传导或通过主要组织相容性复合体I呈递抗原的功能。

研究人员表明，在感应IFNγ时，结肠上皮细胞有效地将病原体和自身来源的抗原呈递给位于上皮屏障的同源上皮内T细胞。上皮细胞的抗原呈递在同源的上皮内T细胞中赋予细胞外ATP酶表达，这限制了细胞外三磷酸腺苷的积累和组织巨噬细胞中NLRP3炎症小体的激活。相反，组织巨噬细胞的抗原呈递以及炎症相关的白细胞介素-1α和白细胞介因子-1β的产生促进了CD4⁺ T细胞在体内致病性转化为粒细胞-巨噬细胞集落刺激因子（GM-CSF）产生的T细胞，从而促进结肠炎和癌症。

总之，这一研究揭示了需要IFNγ传感和上皮细胞抗原呈递的关键检查点，上皮细胞控制体内致病性CD4⁺ T细胞反应的发展。

附：英文原文

Title: Epithelial IFNγ signalling and compartmentalized antigen presentation orchestrate gut immunity

Author: Malik, Ankit, Sharma, Deepika, Aguirre-Gamboa, Ral, McGrath, Shaina, Zabala, Sarah, Weber, Christopher, Jabri, Bana

Issue&Volume: 2023-11-22

Abstract: All nucleated cells express major histocompatibility complex I and interferon‐γ (IFNγ) receptor1, but an epithelial cell-specific function of IFNγ signalling or antigen presentation by means of major histocompatibility complex I has not been explored. We show here that on sensing IFNγ, colonic epithelial cells productively present pathogen and self-derived antigens to cognate intra-epithelial T cells, which are critically located at the epithelial barrier. Antigen presentation by the epithelial cells confers extracellular ATPase expression in cognate intra-epithelial T cells, which limits the accumulation of extracellular adenosine triphosphate and consequent activation of the NLRP3 inflammasome in tissue macrophages. By contrast, antigen presentation by the tissue macrophages alongside inflammasome-associated interleukin-1α and interleukin-1β production promotes a pathogenic transformation of CD4+ T cells into granulocyte–macrophage colony-stimulating-factor (GM-CSF)-producing T cells in vivo, which promotes colitis and colorectal cancer. Taken together, our study unravels critical checkpoints requiring IFNγ sensing and antigen presentation by epithelial cells that control the development of pathogenic CD4+ T cell responses in vivo. IFNγ signalling in epithelial cells promotes antigen presentation that confers intra-epithelial T cells the ability to limit extracellular ATP and consequent NLRP3 inflammasome activation, controlling pathogenic transformation of CD4+ T cells that promotes colitis and colorectal cancer in mouse models.

DOI: 10.1038/s41586-023-06721-1

Source: https://www.nature.com/articles/s41586-023-06721-1

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
官方网址：http://www.nature.com/
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