M1 Macrophage Exosomes MiR-21a-5p Aggravates Inflammatory Bowel Disease Through Decreasing E-cadherin and Subsequent ILC2 Activation
Overview
Molecular Biology
Authors
Affiliations
Abnormal immune regulation is a key feature of the complex pathogenic mechanism of ulcerative colitis (UC). In particular, macrophages and group 2 innate lymphoid cells (ILC2s) are important components of natural immunity that have been shown to play important roles in the pathogenesis of UC, as well as decreased E-cadherin expression on the colonic mucosa. However, it remains unclear how these components interact with each other. In this study, we investigated the molecular mechanisms of UC mediated by macrophage-derived exosomes. We showed for the first time that miR-21a-5p expression is increased in the peritoneal exosomes of mice with dextran sulphate sodium induced enteritis and that miR-21a-5p expression correlates negatively with E-cadherin expression in enterocytes. Moreover, we confirmed that miR-21a-5p was mainly derived from M1 macrophages and demonstrated that KLRG1, a surface inhibitory receptor on ILC2s, participated in excessive ILC2 activation in UC by promoting GATA-3. In conclusion, our results suggest molecular targets and provide a theoretical basis for elucidating the pathogenesis of UC and improving its treatment.
Lialios P, Alimperti S Front Cell Infect Microbiol. 2025; 15:1506636.
PMID: 40007608 PMC: 11850337. DOI: 10.3389/fcimb.2025.1506636.
Macrophage-derived extracellular vesicles as new players in chronic non-communicable diseases.
Lin F, Luo H, Wang J, Li Q, Zha L Front Immunol. 2025; 15:1479330.
PMID: 39896803 PMC: 11782043. DOI: 10.3389/fimmu.2024.1479330.
Li J, Xu J, Huang C, Hu J, Xu H, Guo X Int J Nanomedicine. 2025; 19:13991-14018.
PMID: 39742094 PMC: 11687308. DOI: 10.2147/IJN.S493434.
Ji J, He Q, Xia Y, Sha X, Liang Q, Xu Y J Nanobiotechnology. 2024; 22(1):779.
PMID: 39702207 PMC: 11657265. DOI: 10.1186/s12951-024-03063-6.
Cell-derived biomimetic drug delivery system for inflammatory bowel disease therapy.
Yang W, Lin P, Gao R, Fang Z, Wang Z, Ma Z Mater Today Bio. 2024; 29:101332.
PMID: 39606424 PMC: 11600033. DOI: 10.1016/j.mtbio.2024.101332.