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

易患狼疮的小鼠脾脏 cDC 中 TREM-1 表达增强,且受 miRNA-150 调节

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作者:Sheng Gao, Linbo Yuan, Yongyu Wang, Chunyan Hua

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.

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