Open AccessM1 Macrophage exosomes MiR‐21a‐5p aggravates inflammatory bowel disease through decreasing E‐cadherin and subsequent ILC2 activation
Author(s) -
Lu Jiaxi,
Liu Deliang,
Tan Yuyong,
Deng Feihong,
Li Rong
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16348
Subject(s) - pathogenesis , microvesicles , innate immune system , immunology , macrophage , immune system , innate lymphoid cell , ulcerative colitis , inflammatory bowel disease , cd163 , cadherin , biology , downregulation and upregulation , microrna , cancer research , microbiology and biotechnology , chemistry , disease , medicine , cell , gene , in vitro , biochemistry , genetics
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.