Open AccessSilencing of microRNA‐21 in vivo ameliorates autoimmune splenomegaly in lupus mice
Author(s) -
Garchow Barry G.,
Bartulos Encinas Oscar,
Leung Yiu Tak,
Tsao Patricia Y.,
Eisenberg Robert A.,
Caricchio Roberto,
Obad Susanna,
Petri Andreas,
Kauppinen Sakari,
Kiriakidou Marianthi
Publication year - 2011
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201100171
Subject(s) - autoimmunity , biology , gene silencing , systemic lupus erythematosus , immunology , microrna , cd8 , in vivo , mir 155 , autoantibody , autoimmune disease , microbiology and biotechnology , immune system , cancer research , medicine , disease , genetics , gene , pathology , antibody
MicroRNAs (miRNAs) have been implicated in B cell lineage commitment, regulation of T cell differentiation, TCR signalling, regulation of IFN signalling, and numerous other immunological processes. However, their function in autoimmunity, and specifically in systemic lupus erythematosus (SLE), remains poorly understood. B6.Sle123 is a spontaneous genetic mouse model of SLE characterized by autoantibody production, lymphosplenomegaly, and glomerulonephritis. We identified several differentially regulated miRNAs in B and T lymphocytes of B6.Sle123 mice. We found that miR‐21 expression in lupus B and T cells is up‐regulated and that in vivo silencing of miR‐21 using a tiny seed‐targeting LNA reversed splenomegaly, one of the cardinal manifestations of autoimmunity in B6.Sle123 mice, and de‐repressed PDCD4 expression in vivo and in vitro . In addition, treatment with anti‐miR‐21 altered CD4/CD8 T cell ratios and reduced Fas receptor‐expressing lymphocyte populations. Our study shows that tiny LNAs can be used to efficiently antagonize endogenous miRNAs in peripheral lymphocytes in vivo and in primary lymphocytes cultured ex vivo and can alter the course of a spontaneous genetic disease in mice.