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Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas mouse

Proceedings of the National Academy of Sciences of the United States of America, ISSN: 0027-8424, Vol: 110, Issue: 50, Page: 20194-20199
2013
  • 89
    Citations
  • 0
    Usage
  • 59
    Captures
  • 0
    Mentions
  • 55
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    89
  • Captures
    59
  • Social Media
    55
    • Shares, Likes & Comments
      55
      • Facebook
        55

Article Description

MicroRNA-155 (miR-155) regulates antibody responses and subsequent B-cell effector functions to exogenous antigens. However, the role of miR-155 in systemic autoimmunity is not known. Using the death receptor deficient (Fas ) lupus-prone mouse, we show here that ablation of miR-155 reduced autoantibody responses accompanied by a decrease in serum IgG but not IgM anti-dsDNA antibodies and a reduction of kidney inflammation. MiR-155 deletion in Fas B cells restored the reduced SH2 domain-containing inositol 5′-phosphatase 1 to normal levels. In addition, coaggregation of the Fc γ receptor IIB with the B-cell receptor in miR-155-Fas B cells resulted in decreased ERK activation, proliferation, and production of switched antibodies compared with miR-155 sufficient Fas B cells. Thus, by controlling the levels of SH2 domain-containing inositol 5′-phosphatase 1, miR-155 in part maintains an activation threshold that allows B cells to respond to antigens.

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