英国弗朗西斯·克里克研究所Anne O’Garra团队发现，Blimp-1和c-Maf调节免疫基因网络来防止病原体诱发结肠炎的不同途径。2024年4月12日，《自然—免疫学》杂志在线发表了这项成果。

研究人员利用结肠固有层白细胞（LPL）的单细胞RNA测序以及纯化的CD4⁺ T细胞的RNA-seq和ATAC-seq测序表明，转录因子Blimp-1（由Prdm1编码）和c-Maf共同主要调控Il10，同时负向调控效应T细胞中的促炎细胞因子。感染了肝螺旋杆菌的双缺陷Prdm1^fl/flMaf^fl/flCd4^Cre小鼠会发展成严重的结肠炎，LPL中的TH1/NK/ILC1效应基因会增加，而Prdm1^fl/flCd4^Cre和Maf^fl/flCd4^Cre小鼠则表现出中等程度的病理变化和不太明显的1型效应反应。

来自受感染的Maf^fl/flCd4^Cre小鼠的LPL有更强的17型反应，Il17a和Il22表达增加，粒细胞和髓细胞数量增加，导致T细胞-髓细胞-中性粒细胞相互作用增加。在没有Prdm1或Maf的情况下，人类炎症性肠病中过度表达的基因在感染小鼠的LPL中显示出不同的表达，这揭示了人类疾病的潜在机制。

据介绍，肠道对微生物的免疫反应受细胞因子IL-10的控制，以避免免疫病理。

附：英文原文

Title: Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis

Author: Alvarez-Martinez, Marisol, Cox, Luke S., Pearson, Claire F., Branchett, William J., Chakravarty, Probir, Wu, Xuemei, Slawinski, Hubert, Al-Dibouni, Alaa, Samelis, Vasileios A., Gabryov, Leona, Priestnall, Simon L., Surez-Bonnet, Alejandro, Mikolajczak, Anna, Briscoe, James, Powrie, Fiona, OGarra, Anne

Issue&Volume: 2024-04-12

Abstract: Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4+ Tcells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector Tcells. Double-deficient Prdm1fl/flMaffl/flCd4Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in TH1/NK/ILC1 effector genes in LPLs, while Prdm1fl/flCd4Cre and Maffl/flCd4Cre mice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maffl/flCd4Cre mice had increased type 17 responses with increased Il17a and Il22 expression and an increase in granulocytes and myeloid cell numbers, resulting in increased Tcell–myeloid–neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1 or Maf, revealing potential mechanisms of human disease.

DOI: 10.1038/s41590-024-01814-z

Source: https://www.nature.com/articles/s41590-024-01814-z