Enhanced expression of TREM-1 in splenic cDCs in lupus prone mice and it was modulated by miRNA-150.

Abstract

Over activation of conventional dendritic cells (cDCs) contributes to the development of systemic lupus erythematosus (SLE). Triggering receptor expressed on myeloid cells 1 (TREM-1) is emerging as a potent amplifier of the inflammatory responses. We sought to determine the expression level of TREM-1 on cDCs in a mice model of SLE and to identify miRNA which could modulate TREM-1 expression. In the present study, TREM-1 expression in splenocytes and on cDCs was strongly up-regulated in vivo, and was enhanced with LPS stimulation in vitro. Blockade of TREM-1 signal impaired the TLR4-induced cytokines production. These indicated that TREM-1 potently amplified the function of TLR4 which enhanced the inflammation responses. A common set of dysregulated miRNAs (miRNA-98, -150 and -494) were identified in splenocytes of mice. Moreover, the results of bioinformatics and the immunoblotting, demonstrated that miRNA-150 inhibited the expression of TREM-1. Together, these data suggested that TREM-1 signaling pathway may be a therapeutic target to prevent the effects of the inflammatory cDCs in SLE and miRNA-150 serves as the important regulator.