Mir-17~92 regulates bone marrow homing of plasma cells and production of immunoglobulin G 2c

Mir-17~92 regulates bone marrow homing of plasma cells and production of immunoglobulin G 2c
Title:
Mir-17~92 regulates bone marrow homing of plasma cells and production of immunoglobulin G 2c
Other Titles:
Nature Communications
Keywords:
Publication Date:
17 April 2015
Citation:
Xu S, Ou X, Huo J, et al. Mir-17-92 regulates bone marrow homing of plasma cells and production of immunoglobulin G2c. Nat Commun. 2015;6:6764. Published 2015 Apr 17. doi:10.1038/ncomms7764
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.
License type:
PublisherCopyrights
Funding Info:
This research is supported by Bioprocessing Technology Institute, A*STAR
Description:
ISSN:
2041-1723
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