美国芝加哥大学Bana Jabri等研究人员合作发现，GATA4控制组织免疫的区域化和共生菌驱动的免疫病理学。该项研究成果于2023年1月10日在线发表在《免疫》杂志上。

研究人员发现，转录因子GATA4的区域上皮表达通过调节视黄醇代谢和腔内IgA来控制近端小肠的细菌定植和炎症组织免疫。此外，在没有空肠GATA4表达的小鼠中，共生的节段性丝状细菌促进了致病性的炎症免疫反应，破坏了屏障功能，并在鼠柠檬酸杆菌感染后增加了死亡率。在乳糜泻患者中，GATA4低表达与代谢改变、粘膜放线菌和IL-17免疫增加有关。总之，这些结果揭示了GATA4调节的肠道区域化对细菌定植和组织免疫的广泛影响，并突出了肠道代谢、免疫和微生物群在平衡和疾病中的精心相互依存。

附：英文原文

Title: GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology

Author: Zachary M. Earley, Wioletta Lisicka, Joseph J. Sifakis, Raúl Aguirre-Gamboa, Anita Kowalczyk, Jacob T. Barlow, Dustin G. Shaw, Valentina Discepolo, Ineke L. Tan, Saideep Gona, Jordan D. Ernest, Polly Matzinger, Luis B. Barreiro, Andrey Morgun, Albert Bendelac, Rustem F. Ismagilov, Natalia Shulzhenko, Samantha J. Riesenfeld, Bana Jabri

Issue&Volume: 2023/01/10

Abstract: There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA. Furthermore, in mice without jejunal GATA4 expression, the commensal segmented filamentous bacteria promoted pathogenic inflammatory immune responses that disrupted barrier function and increased mortality upon Citrobacter rodentium infection. In celiac disease patients, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. Taken together, these results reveal broad impacts of GATA4-regulated intestinal regionalization on bacterial colonization and tissue immunity, highlighting an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease.

DOI: 10.1016/j.immuni.2022.12.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00645-8#secsectitle0010