title: miR-182 is largely dispensable for adaptive immunity: lack of correlation between expression and function.
abstract: MicroRNA (miR)-mediated regulation of protein abundance is a pervasive mechanism of directing cellular processes. The well-studied and abundant miR-182 has previously been implicated in many aspects of T cell function, DNA repair, and cancer. In this study, we show that miR-182 is the most highly induced miR in B cells undergoing class-switch recombination. To elucidate the requirement of miR-182 in lymphocyte function, we extensively characterized mice with a targeted deletion of Mir182. We show that despite its dramatic induction, loss of miR-182 has minimal impact on B cell development, the ability of B cells to undergo class-switch recombination ex vivo and to undergo Ag-driven affinity maturation in vivo. Furthermore, in striking contrast to knockdown studies that demonstrated the requirement of miR-182 in T cell function, miR-182-deficient mice display no defect in T cell development and activation. Finally, we show that T cell-dependent immune response to experimental Listeria monocytogenes infection is intact in miR-182-deficient mice. We conclude that, contrary to previous studies, miR-182 does not play a significant role in all measured aspects of mouse adaptive immunity. This striking absence of a phenotype highlights the lack of correlation between expression pattern and functional requirement, underscores the limitations of using knockdown approaches to assess miR requirements, and suggests that miR networks may compensate for the chronic loss of specific miRs.
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, Gerstner Sloan Kettering Graduate School, New York, NY 10065;
authors: Joseph N
authors: JN
authors: Pucella
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, Gerstner Sloan Kettering Graduate School, New York, NY 10065; Immunology and Microbial Pathogenesis Program, Weill-Cornell Graduate School of Medical Sciences, New York, NY 10065;
authors: Wei-Feng
authors: WF
authors: Yen
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, Gerstner Sloan Kettering Graduate School, New York, NY 10065; Immunology and Microbial Pathogenesis Program, Weill-Cornell Graduate School of Medical Sciences, New York, NY 10065;
authors: Myoungjoo V
authors: MV
authors: Kim
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, Gerstner Sloan Kettering Graduate School, New York, NY 10065; Immunology and Microbial Pathogenesis Program, Weill-Cornell Graduate School of Medical Sciences, New York, NY 10065;
authors: Joris
authors: J
authors: van der Veeken
authors: Chong T
authors: CT
authors: Luo
authors: Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY 10065; and.
authors: Nicholas D
authors: ND
authors: Socci
authors: Department of Genomic Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors: Yukiko
authors: Y
authors: Naito
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, Gerstner Sloan Kettering Graduate School, New York, NY 10065; Immunology and Microbial Pathogenesis Program, Weill-Cornell Graduate School of Medical Sciences, New York, NY 10065;
authors: Ming O
authors: MO
authors: Li
authors: Department of Genomic Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors: Naoharu
authors: N
authors: Iwai
authors: Immunology Program, Memorial Sloan Kettering Cancer Center, Gerstner Sloan Kettering Graduate School, New York, NY 10065; Immunology and Microbial Pathogenesis Program, Weill-Cornell Graduate School of Medical Sciences, New York, NY 10065; chaudhuj@mskcc.org.
authors: Jayanta
authors: J
authors: Chaudhuri
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology / Q000502:physiology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C540524:Mirn182 microRNA, mouse