title: Mir-17-92 regulates bone marrow homing of plasma cells and production of immunoglobulin G2c.
abstract: The polycistronic mir-17-92 cluster, also known as oncomir-1, was previously shown to be essential for early B lymphopoiesis. However, its role in late-stage B-cell differentiation and function remains unexplored. Here we ablate mir-17-92 in mature B cells and demonstrate that mir-17-92 is dispensable for conventional B-cell development in the periphery. Interestingly, mir-17-92-deficiency in B cells leads to enhanced homing of plasma cells to the bone marrow during T-cell-dependent immune response and selectively impairs IgG2c production. Mechanistically, mir-17-92 directly represses the expression of Sphingosine 1-phosphate receptor 1 and transcription factor IKAROS, which are, respectively, important for plasma cell homing and IgG2c production. We further show that deletion of mir-17-92 could reduce IgG2c anti-DNA autoantibody production and hence mitigate immune complex glomerulonephritis in Shp1-deficient mice prone to autoimmunity. Our results identify important roles for mir-17-92 in the regulation of peripheral B-cell function.
authors.affiliation: 1] Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668 [2] Department of Physiology, National University of Singapore, Singapore, Singapore 117597.
authors.forename: Shengli
authors.initials: S
authors.lastname: Xu
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668.
authors.forename: Xijun
authors.initials: X
authors.lastname: Ou
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Huo
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668.
authors.forename: Kristen
authors.initials: K
authors.lastname: Lim
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668.
authors.forename: Sheena
authors.initials: S
authors.lastname: Chee
authors.affiliation: 1] Bioprocessing Technology Institute, Agency for Science, Technology and Research (A-STAR), Singapore 138668 [2] Department of Physiology, National University of Singapore, Singapore, Singapore 117597 [3] Department of Microbiology, National University of Singapore, Singapore 117545.
authors.forename: Kong-Peng
authors.initials: KP
authors.lastname: Lam
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism; D007105:Immune Complex Diseases / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs; D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse