中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Brg1-imprinted chromatin status controls effector and memory group 2 innate lymphoid cell metabolism to exacerbate allergic lung inflammation

文献类型：期刊论文

作者Tang, Jupei7; Sun, Hanxiao5; Chang, Huidan6; Yuan, Liyun6; Chen, Yue7; Zhang, Xueliang3; Tao, Yongzhen7; Yang, Lifeng7; Shao, Zhen7; Guo, Xiaohuan1,2
刊名JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
出版日期2026
卷号157期号:1页码:21
关键词Group 2 innate lymphoid cell (ILC2) Brg1 allergic lung inflammation ILC2 memory chromatin accessibility glycolysis
ISSN号0091-6749
DOI10.1016/j.jaci.2025.08.029
通讯作者Qiu, Jinxin(jxqiu@sinh.ac.cn) ; Qin, Jun(qinjun@sinh.ac.cn) ; Qiu, Ju(qiuju@sinh.ac.cn)
英文摘要Background: The chromatin status fluctuates with effector and memory group 2 innate lymphoid cell (ILC2) responses. How this intricate coordination affects allergic lung inflammation remains unclear. Objective: We examined how the chromatin remodeler brahmarelated gene 1 (Brg1) regulates ILC2s in allergic lung inflammation. Methods: Acute lung allergic inflammation was induced with papain in wild-type, Il5(Cre/+)Smarca(4flox/flox) (Smarca(4f/f)), Il5(Cre/+)Hif1a(f/f), and Il5(Cre/+)Ldha(f/f) mice. Secondary lung inflammation was induced with low-dose IL-33 in papainprimed Il5(Cre/+)Smarca4(f/f) mice. ATAC-Seq, RNA sequencing, and Brg1 CUT&Tag analyses were performed on naive ILC2s, effector ILC2s (ILC2(eff)), memory ILC2s (ILC2(mem)), IL-33-challenged Brg1-deficient ILC2s, Brg1-deficient ILC2(mem), and human ILC2s treated with or without the Brg1 inhibitor Compound 14. ILC2 metabolism was analyzed by C-13 glucose isotype tracing and metabolic flux, Seahorse, and SCENITH assays. Compound 14 was used to treat mouse and humanized mouse models of allergic lung inflammation. Results: Brg1 expression was upregulated in asthma patients' ILC2s and was induced by IL-33. Brg1 promoted IL-5(+) and IL-13(+) ILC2 expansion and exacerbated both acute and secondary lung inflammation. Brg1 imprinted the chromatin landscape favoring aerobic glycolysis, the metabolic process reinforced in ILC2(eff) and ILC2(mem). Brg1-augmented Hif1a enhancer accessibility was a sustained epigenetic signature in ILC2(mem) inherited from ILC2(eff), and Hif1 alpha enhanced ILC2(ef)f and ILC2(mem) responses. Pharmacologic inhibition of Brg1, rather than dexamethasone treatment, in acute phase alleviated secondary lung inflammation. Conclusion: Brg1 promotes the expansion of pathogenic ILC2(eff) and ILC2(mem) and exacerbates allergic lung inflammation. Mechanistically, Brg1 increases the chromatin accessibility and transcription of Hif1a and Ldha, key factors reinforcing ILC2 glycolysis metabolism.
WOS关键词CYTOKINES
WOS研究方向Allergy ; Immunology
语种英语
WOS记录号WOS:001659968700001
出版者MOSBY-ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/322646]  
专题中国科学院上海药物研究所
通讯作者Qiu, Jinxin; Qin, Jun; Qiu, Ju
作者单位1.Tsinghua Univ, Beijing Key Lab Immunol Res Chron Dis, Beijing, Peoples R China
2.Tsinghua Univ, Inst Immunol, Sch Med, Beijing, Peoples R China
3.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Sch Med, Dept Rheumatol & Immunol, Shanghai, Peoples R China
4.Shanghai Jiao Tong Univ, Key Lab Cell Differentiat & Apoptosis, Shanghai Inst Immunol,Dept Immunol & Microbiol, Chinese Minist Educ,Sch Med, Shanghai, Peoples R China
5.Tongren Hosp, Dept Lab Med, Beijing, Peoples R China
6.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Biomed Big Data Ctr, Shanghai, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, Unit Resp Immun & Infect, Shanghai, Peoples R China
9.Anhui Med Univ, Sch Life Sci, Hefei, Peoples R China
推荐引用方式
GB/T 7714		 Tang, Jupei,Sun, Hanxiao,Chang, Huidan,et al. Brg1-imprinted chromatin status controls effector and memory group 2 innate lymphoid cell metabolism to exacerbate allergic lung inflammation[J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,2026,157(1):21.
APA Tang, Jupei.,Sun, Hanxiao.,Chang, Huidan.,Yuan, Liyun.,Chen, Yue.,...&Qiu, Ju.(2026).Brg1-imprinted chromatin status controls effector and memory group 2 innate lymphoid cell metabolism to exacerbate allergic lung inflammation.JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,157(1),21.
MLA Tang, Jupei,et al."Brg1-imprinted chromatin status controls effector and memory group 2 innate lymphoid cell metabolism to exacerbate allergic lung inflammation".JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 157.1(2026):21.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。