MicroRNAs (miR16 and miR146a) regulation of lupus development in NZB/W F1 mouse model (167.11)

• Published in: The Journal of immunology (1950) 2011-04, Vol.186 (1_Supplement), p.167-167.11
• Main Authors: Yuan, Yao, Kotenko, Serguei, Laurindo, Fernanda, Salerno, Erica, Raveche, Elizabeth
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.186.Supp.167.11

SLE is a heterogeneous autoimmune disease and the specific cause remains unknown. IFNα has well defined positive effects in lupus disease development and by delivering exogenous IFNα to NZB/W F1 mouse accelerated lupus manifestations. Yet the effects of IFNλ, sharing partially common signaling pathways with IFNα, remains unknown in lupus. In the study, we treated B/W mice with IFNα or IFNλ for 12 week period and IFNα treated group developed much earlier and more severe lupus-disease than others. Moreover, combination with both cytokines enhanced the effects of either single treatment. At the time when only IFNα treated group developed proteinuria, this group of mice showed a pronounced decrease in regulatory B cells (B10)than others, in contrast, IFNλ treated group showed an expansion of B10. Furthmore, we wanted to investigate whether or not, as consequences of IFNs treatment, any specific microRNAs could be responsible for the cell type changes. In these B/W mice, splenic RNA were taken for microRNA microarray analysis. Results showed a few miRNAs up or downregulated in IFNs treated groups. To validate the result, miR16 and miR-146a were selected for realtime PCR.We found that almost in consistence with microarray, IFNλ treated had elevated level of both miRNAs than control, however, IFNα treated group showed underexpression of both miRNAs. Thus, it is likely that abnormal miRNAs changes due to IFNs treatment may drive the disease development in the lupus-prone B/W mice.