Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Runtsch, MC; Hu, R; Alexander, M; Wallace, J; Kagele, D; Petersen, C; Valentine, JF; Welker, NC; Bronner, MP; Chen, X; Smith, DP; Ajami, NJ; Petrosino, JF; Round, JL; O'Connell, RM.
MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis.
Oncotarget. 2015; 6(30): 28556-72.
Doi: 10.18632/oncotarget.5597
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- Führende Autor*innen der Med Uni Graz
- Runtsch Marah
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- Abstract:
- Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a-/- mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a-/- mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Colitis - chemically induced, genetics, immunology, metabolism, microbiology, pathology, prevention & control
- Colon - immunology, metabolism, microbiology, pathology
- Dextran Sulfate - administration & dosage
- Disease Models, Animal - administration & dosage
- Fecal Microbiota Transplantation - administration & dosage
- Gastrointestinal Microbiome - immunology
- Gene Expression Regulation - administration & dosage
- Genetic Predisposition to Disease - administration & dosage
- Host-Pathogen Interactions - administration & dosage
- Immunity, Mucosal - administration & dosage
- Inflammation Mediators - immunology, metabolism
- Mice, Inbred C57BL - administration & dosage
- Mice, Knockout - administration & dosage
- MicroRNAs - genetics, immunology, metabolism
- Phenotype - administration & dosage
- Signal Transduction - administration & dosage
- T-Lymphocyte Subsets - immunology, metabolism
- Time Factors - administration & dosage
- Find related publications in this database (Keywords)
- miRNA
- miR-146a
- intestine
- microbiota
- colitis