title: Defective germinal center B-cell response and reduced arthritic pathology in microRNA-29a-deficient mice.
abstract: MicroRNA (miR) are short non-coding RNA sequences of 19-24 nucleotides that regulate gene expression by binding to mRNA target sequences. The miR-29 family of miR (miR-29a, b-1, b-2 and c) is a key player in T-cell differentiation and effector function, with deficiency causing thymic involution and a more inflammatory T-cell profile. However, the relative roles of different miR-29 family members in these processes have not been dissected. We studied the immunological role of the individual members of the miR-29 family using mice deficient for miR-29a/b-1 or miR-29b-2/c in homeostasis and during collagen-induced arthritis. We found a definitive hierarchy of immunological function, with the strong phenotype of miR-29a-deficiency in thymic involution and T-cell activation being reduced or absent in miR-29c-deficient mice. Strikingly, despite elevating the Th1 and Th17 responses, loss of miR-29a conferred near-complete protection from collagen-induced arthritis (CIA), with profound defects in B-cell proliferation and antibody production. Our results identify the hierarchical structure of the miR-29 family in T-cell biology, and identify miR-29a in B cells as a potential therapeutic target in arthritis.
authors.affiliation: VIB Center for Brain and Disease Research, VIB, KU Leuven Campus Gasthuisberg, Herestraat 49, bus 1026, 3000, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Annemarie
authors.initials: A
authors.lastname: van Nieuwenhuijze
authors.affiliation: VIB Center for Brain and Disease Research, VIB, KU Leuven Campus Gasthuisberg, Herestraat 49, bus 1026, 3000, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.affiliation: VIB Center for Brain and Disease Research, VIB, KU Leuven Campus Gasthuisberg, Herestraat 49, bus 1026, 3000, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Humblet-Baron
authors.affiliation: VIB Center for Brain and Disease Research, VIB, KU Leuven Campus Gasthuisberg, Herestraat 49, bus 1026, 3000, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Jayasree
authors.initials: J
authors.lastname: Sreenivasan
authors.affiliation: Experimental Rheumatology, Radboud University Medical Center, 6525, Nijmegen, GA, The Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Koenders
authors.affiliation: VIB Center for Brain and Disease Research, VIB, KU Leuven Campus Gasthuisberg, Herestraat 49, bus 1026, 3000, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Schlenner
authors.affiliation: Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge, CB22 3AT, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Linterman
authors.affiliation: VIB Center for Brain and Disease Research, VIB, KU Leuven Campus Gasthuisberg, Herestraat 49, bus 1026, 3000, Leuven, Belgium. adrian.liston@vib.be.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. adrian.liston@vib.be.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D018858:Germinal Center / Q000187:drug effects / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism
chemical_list: C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D011070:Poly I-C
keywords: Autoimmune pathology; Experimental arthritis; MicroRNA; Thymic involution