Cell子刊：GATA4或调控肠道的免疫功能区域化
- ①转录因子GATA4在小肠的表达具有区域化特征，在十二指肠和空肠的上皮细胞表达，但在回肠或结肠则不表达；
- ②GATA4的局部化表达通过调节视黄醇代谢和肠腔IgA，控制近端小肠细菌定植和炎症组织免疫；
- ③在空肠GATA4缺失的小鼠中，共生的分段丝状细菌(SFB)促进致病性炎症性免疫反应，破坏了屏障功能，增加了柠檬酸杆菌感染导致的死亡率；
- ④在乳糜泻患者中，GATA4低表达与代谢改变、放线杆菌感染和IL-17免疫增加有关。
主编推荐语
肠道中的细菌定植和免疫力具有区域化的特征，对健康和疾病具有重要作用，但其中的机制尚不清楚。Immunity近期发表的文章，发现转录因子GATA4在小肠的表达具有区域化分布特征，其通过调控代谢和肠腔的IgA来控制粘附细菌的定植。同时，正确的肠道区域化和共生菌定植对于预防人和小鼠的Th17反应失调和免疫病理至关重要。
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GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology
GATA4控制组织免疫区域化和共生菌驱动的免疫病理
10.1016/j.immuni.2022.12.009
01-10, Article
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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.
First Authors:
Zachary M Earley
Correspondence Authors:
Samantha J Riesenfeld,Bana Jabri
All Authors:
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
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