Frontiers in immunology, 2019-01, Vol.9, p.3118-3118
2019
Details
- Autor(en) / Beteiligte
- Titel
- Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages
- Ist Teil von
- Frontiers in immunology, 2019-01, Vol.9, p.3118-3118
- Ort / Verlag
- Switzerland: Frontiers Media S.A
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Intestinal macrophages are highly mobile cells with extraordinary plasticity and actively contribute to cytokine-mediated epithelial cell damage. The mechanisms triggering macrophage polarization into a proinflammatory phenotype are unknown. Here, we report that during inflammation macrophages enhance its intercellular adhesion properties in order to acquire a M1-phenotype. Using and models we demonstrate that intercellular adhesion is mediated by integrin-αVβ3 and relies in the presence of the unconventional class I myosin 1F (Myo1F). Intercellular adhesion mediated by αVβ3 stimulates M1-like phenotype in macrophages through hyperactivation of STAT1 and STAT3 downstream of ILK/Akt/mTOR signaling. Inhibition of integrin-αVβ3, Akt/mTOR, or lack of Myo1F attenuated the commitment of macrophages into a pro-inflammatory phenotype. In a model of colitis, Myo1F deficiency strongly reduces the secretion of proinflammatory cytokines, decreases epithelial damage, ameliorates disease activity, and enhances tissue repair. Together our findings uncover an unknown role for Myo1F as part of the machinery that regulates intercellular adhesion and polarization in macrophages.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1664-3224eISSN: 1664-3224DOI: 10.3389/fimmu.2018.03118Titel-ID: cdi_doaj_primary_oai_doaj_org_article_53984ed54b9949d3820f639513674efb
- Format
- –
- Schlagworte
- Akt/mTOR/STAT signaling, Animals, Cell Line, Tumor, Colitis, Ulcerative - chemically induced, Colitis, Ulcerative - immunology, Cytoskeleton - immunology, Cytoskeleton - metabolism, Dextran Sulfate - administration & dosage, Dextran Sulfate - toxicity, Disease Models, Animal, Humans, Immunology, inflammation, Integrin alphaVbeta3 - immunology, Integrin alphaVbeta3 - metabolism, intercellular adhesion, Interleukin-1beta - immunology, Interleukin-1beta - metabolism, M1-polarization, Macrophage Activation, Macrophages - immunology, Macrophages - metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, myosin 1F, Myosin Type I - genetics, Myosin Type I - immunology, Myosin Type I - metabolism, Primary Cell Culture, RAW 264.7 Cells