PMID- 38022496 OWN - NLM STAT- MEDLINE DCOM- 20231204 LR - 20240325 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - The transcription factor ELF4 alleviates inflammatory bowel disease by activating IL1RN transcription, suppressing inflammatory TH17 cell activity, and inducing macrophage M2 polarization. PG - 1270411 LID - 10.3389/fimmu.2023.1270411 [doi] LID - 1270411 AB - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder affecting millions worldwide. Due to the complexity of its pathogenesis, the treatment options for IBD are limited. This study focuses on ELF4, a member of the ETS transcription factor family, as a target to elucidate its role in IBD and investigate its mechanism of action in alleviating IBD symptoms by activating IL1RN transcription to suppress the activity of inflammatory TH17 cells. METHODS: Using the GEO database, this study examined LPS-induced intestinal inflammatory genes and their regulation mechanisms. We examined the colon length of LPS-treated mice and derived the Disease Activity Index (DAI). H&E staining, ELISA, and flow cytometry were used to detect mice colon tissue damage, inflammatory factor levels in mouse serum, mouse macrophage types and inflammatory TH17 cell activity. RT-qPCR and Western blot detected ELF4, IL1RN, M1, and M2 polarization markers. In Vitro, using dual-luciferase and ChIP assays, we tested mouse bone marrow-derived macrophages (BMDMs) and mouse intestinal epithelial cells for IL1RN promoter activity and ELF4 enrichment. RESULTS: Bioinformatics showed that LPS-induced colitis animals have reduced ELF4 expression in their colon tissue. In vivo tests confirmed reduced ELF4 expression in mice with LPS-induced colitis. ELF4 overexpression reduced mouse intestinal inflammation. ELF4 activated IL1RN transcription in bioinformatics and in vitro tests. ELF4 promoted IL1RN transcription and macrophage M2 polarization to limit intestinal epithelial cell death and inflammation and reduce mouse intestinal inflammation in vitro. ELF4 also reduced the Th17/Treg ratio by increasing IL1RN transcription. CONCLUSION: ELF4 activates IL1RN transcription, suppresses inflammatory TH17 cells, and induces macrophage M2 polarization to treat IBD. CI - Copyright (c) 2023 Cao, Chen, Peng, Cheng, Xie, Hou, Chen, Ye, Li, Wang, Ren, Xiong, Geng and Gong. FAU - Cao, Meiwan AU - Cao M AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Chen, Peiyu AU - Chen P AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Peng, Baoling AU - Peng B AD - Center for Child Health and Mental Health, Shenzhen Childen's Hospital, Shenzhen, China. FAU - Cheng, Yang AU - Cheng Y AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Xie, Jing AU - Xie J AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Hou, Ziang AU - Hou Z AD - Department of Internal, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Chen, Huan AU - Chen H AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Ye, Liping AU - Ye L AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Li, Huiwen AU - Li H AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Wang, Hongli AU - Wang H AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Ren, Lu AU - Ren L AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Xiong, Liya AU - Xiong L AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Geng, Lanlan AU - Geng L AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. FAU - Gong, Sitang AU - Gong S AD - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231106 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Lipopolysaccharides) RN - 0 (Transcription Factors) RN - 0 (Il1rn protein, mouse) RN - 0 (Elf4 protein, mouse) SB - IM MH - Animals MH - Mice MH - Cell Differentiation/genetics MH - *Colitis/chemically induced MH - Inflammation/genetics/metabolism MH - *Inflammatory Bowel Diseases/genetics/metabolism MH - Lipopolysaccharides/adverse effects MH - Macrophages/metabolism MH - Th17 Cells MH - Transcription Factors/genetics/metabolism PMC - PMC10657822 OTO - NOTNLM OT - IL1RN OT - Th17 cells OT - bioinformatics analysis OT - disease activity index OT - inflammatory bowel disease OT - inflammatory factors OT - macrophage M2 polarization OT - transcription regulator ELF4 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/11/29 18:43 MHDA- 2023/12/01 06:44 PMCR- 2023/01/01 CRDT- 2023/11/29 15:24 PHST- 2023/07/31 00:00 [received] PHST- 2023/10/06 00:00 [accepted] PHST- 2023/12/01 06:44 [medline] PHST- 2023/11/29 18:43 [pubmed] PHST- 2023/11/29 15:24 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1270411 [doi] PST - epublish SO - Front Immunol. 2023 Nov 6;14:1270411. doi: 10.3389/fimmu.2023.1270411. eCollection 2023.