近日，美国辛辛那提大学Theresa Alenghat及其小组发现，源于微生物群的丁酸盐通过组蛋白去乙酰化酶3限制簇细胞分化，来调节肠道2型免疫力。2024年1月30日，国际知名学术期刊《免疫》在线发表了这一成果。

研究人员揭示了微生物群对肠道簇细胞生物学的影响。随着肠道微生物群的消失，簇细胞和2型先天性淋巴细胞的琥珀酸诱导率升高。定殖产生丁酸盐的细菌或用丁酸盐处理可抑制这种效应，并降低肠道组蛋白去乙酰化酶的活性。表观遗传修饰酶组蛋白去乙酰化酶3（HDAC3）的上皮缺失抑制了体内簇细胞的扩张，并损害了蠕虫感染期间的2型免疫反应。

丁酸盐限制了干细胞分化为簇细胞，而抑制成年小鼠和人类肠器官组织中的HDAC3会阻止簇细胞的扩张。总之，这些数据确定了干细胞中的HDAC3机制，即受共生代谢物抑制的簇细胞分化，并揭示了微生物群校准肠道2型免疫的途径。

据介绍，粘膜组织中的簇细胞是2型免疫的关键调节因子。

附：英文原文

Title: Microbiota-derived butyrate restricts tuft cell differentiation via histone deacetylase 3 to modulate intestinal type 2 immunity

Author: Emily M. Eshleman, Taylor Rice, Crystal Potter, Amanda Waddell, Seika Hashimoto-Hill, Vivienne Woo, Sydney Field, Laura Engleman, Hee-Woong Lim, Michael A. Schumacher, Mark R. Frey, Lee A. Denson, Fred D. Finkelman, Theresa Alenghat

Issue&Volume: 2024-01-30

Abstract: Tuft cells in mucosal tissues are key regulators of type 2 immunity. Here, we examinedthe impact of the microbiota on tuft cell biology in the intestine. Succinate inductionof tuft cells and type 2 innate lymphoid cells was elevated with loss of gut microbiota.Colonization with butyrate-producing bacteria or treatment with butyrate suppressedthis effect and reduced intestinal histone deacetylase activity. Epithelial-intrinsicdeletion of the epigenetic-modifying enzyme histone deacetylase 3 (HDAC3) inhibitedtuft cell expansion in vivo and impaired type 2 immune responses during helminth infection. Butyrate restrictedstem cell differentiation into tuft cells, and inhibition of HDAC3 in adult mice andhuman intestinal organoids blocked tuft cell expansion. Collectively, these data definea HDAC3 mechanism in stem cells for tuft cell differentiation that is dampened bya commensal metabolite, revealing a pathway whereby the microbiota calibrate intestinaltype 2 immunity.

DOI: 10.1016/j.immuni.2024.01.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00027-X