Transcriptomic analysis of pathways associated with αv integrin-related non-canonical autophagy in human B cells
Transcriptomic analysis of pathways associated with αv integrin-related non-canonical autophagy in human B cells
Abstract Autophagy proteins have been linked with development of immune-mediated diseases including lupus, but the mechanisms for this are unclear. We have previously shown that non-canonical autophagy induced by αv-integrins regulates B cell activation by viral and self-antigens in mice. Here we investigated the involvement of this pathway in B cells from human tissue. Our data revealed that autophagy is specifically induced in germinal-center and memory B cell sub-populations from human tonsil and spleen. Transcriptomic analysis showed that induction of autophagy is related to unique aspects of activated B cells such as mitochondrial metabolism. To understand the function of non-canonical autophagy in B cells, we used CRISPR-mediated knockdown of autophagy genes. Integrating data from primary B cells and knockout cells we found that αv-integrin-related non-canonical autophagy limits activation of specific pathways while promoting others. These data provide new mechanistic links for autophagy and immune dysregulation in diseases such as lupus.
Muir Virginia、Suchland Emmaline、Tam Jenny M.、Garner Ethan C.、Lacy-Hulbert Adam、Giltiay Natalia、James Richard G.、Sagadiev Sara、Meitlis Iana、Shows Donna、Wivagg Carl N、Acharya Mridu
Immunology Program, Benaroya Research Institute at Virginia MasonSeattle Children?ˉs Research InstituteWyss Institute for Biologically Inspired Engineering, Harvard University||Department of Genetics, Harvard Medical SchoolDepartment of Molecular and Cell Biology, Harvard UniversityImmunology Program, Benaroya Research Institute at Virginia Mason||Departments of Immunology, University of WashingtonDepartments of Rheumatology, University of WashingtonSeattle Children?ˉs Research Institute||Departments of Pediatrics, University of Washington||Departments of Pharmacology, University of WashingtonImmunology Program, Benaroya Research Institute at Virginia Mason||Seattle Children?ˉs Research InstituteSeattle Children?ˉs Research InstituteImmunology Program, Benaroya Research Institute at Virginia MasonDepartment of Molecular and Cell Biology, Harvard UniversityImmunology Program, Benaroya Research Institute at Virginia Mason||Seattle Children?ˉs Research Institute||Departments of Pediatrics, University of Washington
基础医学生物科学研究方法、生物科学研究技术分子生物学
Muir Virginia,Suchland Emmaline,Tam Jenny M.,Garner Ethan C.,Lacy-Hulbert Adam,Giltiay Natalia,James Richard G.,Sagadiev Sara,Meitlis Iana,Shows Donna,Wivagg Carl N,Acharya Mridu.Transcriptomic analysis of pathways associated with αv integrin-related non-canonical autophagy in human B cells[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2021.08.02.452710.点此复制
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