Defective germinal center B-cell response and reduced arthritic pathology in microRNA-29a-deficient mice View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-06

AUTHORS

Annemarie van Nieuwenhuijze, James Dooley, Stéphanie Humblet-Baron, Jayasree Sreenivasan, Marije Koenders, Susan M. Schlenner, Michelle Linterman, Adrian Liston

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. More... »

PAGES

2095-2106

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00018-017-2456-6

DOI

http://dx.doi.org/10.1007/s00018-017-2456-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1074188639

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28124096


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