Menin orchestrates macrophage reprogramming to maintain the pulmonary immune homeostasis.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-01-15 DOI:10.1016/j.celrep.2024.115219

Xingwen Zhu, Bin Xu, Aobo Lian, Xiaoqian Zhang, Yiting Wang, Yuan Zhang, Li Zhang, Jie Ma, Shubin Gao, Guanghui Jin

{"title":"Menin orchestrates macrophage reprogramming to maintain the pulmonary immune homeostasis.","authors":"Xingwen Zhu, Bin Xu, Aobo Lian, Xiaoqian Zhang, Yiting Wang, Yuan Zhang, Li Zhang, Jie Ma, Shubin Gao, Guanghui Jin","doi":"10.1016/j.celrep.2024.115219","DOIUrl":null,"url":null,"abstract":"<p><p>Menin is a scaffold protein encoded by the Men1 gene, and it interacts with a variety of chromatin regulators to activate or repress cellular processes. The potential importance of menin in immune regulation remains unclear. Here, we report that myeloid deletion of Men1 results in the development of spontaneous pulmonary alveolar proteinosis (PAP). This is strongly correlated with impaired development of alveolar macrophages (AM) through inactivation of the granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) pathway caused by Men1 deficiency. Mechanistically, menin directly interacts with the SET domain containing 2 (SETD2) through the N-terminal domain (NTD) and Palm domains to maintain protein stability and chromatin recruitment. SETD2 and menin collectively maintain CSF2 expression through H3K36me3, which orchestrates AM reprogramming and pulmonary immune homeostasis. Targeting H3K36me3 remodeling mitigated the aberrant activation of macrophages caused by lipopolysaccharide (LPS). Our results point to a nonredundant role of menin in the control of macrophage lineage maintenance via reinforcement of the H3K36me3 transcriptional program.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115219"},"PeriodicalIF":7.5000,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2024.115219","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Menin is a scaffold protein encoded by the Men1 gene, and it interacts with a variety of chromatin regulators to activate or repress cellular processes. The potential importance of menin in immune regulation remains unclear. Here, we report that myeloid deletion of Men1 results in the development of spontaneous pulmonary alveolar proteinosis (PAP). This is strongly correlated with impaired development of alveolar macrophages (AM) through inactivation of the granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) pathway caused by Men1 deficiency. Mechanistically, menin directly interacts with the SET domain containing 2 (SETD2) through the N-terminal domain (NTD) and Palm domains to maintain protein stability and chromatin recruitment. SETD2 and menin collectively maintain CSF2 expression through H3K36me3, which orchestrates AM reprogramming and pulmonary immune homeostasis. Targeting H3K36me3 remodeling mitigated the aberrant activation of macrophages caused by lipopolysaccharide (LPS). Our results point to a nonredundant role of menin in the control of macrophage lineage maintenance via reinforcement of the H3K36me3 transcriptional program.

查看原文本刊更多论文

Menin协调巨噬细胞重编程以维持肺免疫稳态。

Menin是一种由Men1基因编码的支架蛋白，它与多种染色质调节因子相互作用，激活或抑制细胞过程。menin在免疫调节中的潜在重要性尚不清楚。在这里，我们报道Men1的髓系缺失导致自发性肺泡蛋白沉积症（PAP）的发展。这与Men1缺乏引起的粒细胞-巨噬细胞集落刺激因子（GM-CSF/CSF2）通路失活导致肺泡巨噬细胞（AM）发育受损密切相关。在机制上，menin通过n端结构域（NTD）和Palm结构域直接与含有2的SET结构域（SETD2）相互作用，以维持蛋白质稳定性和染色质募集。SETD2和menin共同通过H3K36me3维持CSF2的表达，H3K36me3协调AM重编程和肺免疫稳态。靶向H3K36me3重塑可减轻脂多糖（LPS）引起的巨噬细胞异常活化。我们的研究结果表明menin通过增强H3K36me3转录程序在控制巨噬细胞谱系维持中的非冗余作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.