Table 1.

The roles of miRNAs in the pathogenesis of SLE.

Events	miRNA	Levels	Mechanism	Biological function	Experimental subject	Reference
DCs	let-7c	↑	suppresses SOCS1 expression	contributes to a broad spectrum of proinflammatory DC phenotype	DCBlimp1ko mice	(23)
	miR-155	↑	enhances TLR7-induced CD40 expression	contributes to the hyperactivated TLR7 response in lupus pDCs	Lupus-Prone NZB/W F1 mice	(25)
	miR-150	↓	inhibits the expression of TREM-1	enhances the inflammation responses in splenic cDCs in lupus prone mice	MRLlpr/lpr mice and C57BL/6 wild type mice	(26)
B cell	miR-1246	↓	reduces the inhibitory effect on the expression of EBF1 and activates AKT signaling pathway	contributes to the development, activation, and proliferation of B cells	PBMCs from SLE patients and healthy controls	(47)
	miR-15a	↑	targets important genes involving cell cycle (e.g. cyclin D1) or cell apoptosis (e.g. Bcl-2)	disrupts the balance between regulatory B cells (B-10) and the pathogenic B cells (B-2) and increases the anti-dsDNA autoantibody levels	SLE mouse model	(46)
	miR-30a	↑	decreases the expression of Lyn such as CD19 and CD180	regulates the B cell proliferation and antibody production	PBMCs from SLE patients and healthy controls	(40)
	hsa-miR-345	↑	inhibits IRF8	regulates the differentiation of B cells	PBMCs from SLE patients and healthy controls	(97)
	hsa-miR-224	↑	contributes to IRF4 overexpression and increass production of IL-21	B cell hyperresponsiveness
	hsa-miR-10a	↑	inhibits IL-8 during the inactive phase	blocks the generation of autoreactive antibodies by B lymphocytes
	miR-155	↑	contributes to the reduction of SHIP-1 expression partly	increases serum IgG anti-dsDNA antibodies and kidney inflammation	Faslpr lupus-prone mice and their PBMCs	(38)
			increases the expression of PU.1 and TNF-α, which in turn promotes BAFF and CD19 protein expression	disrupts peripheral tolerance in B cells and thereby induces autoantibody production increase the SLEDAI-2K	PBMCs from SLE patients and healthy controls	(39)
	miR-152-3p	↑	increases the BAFF expression by targeting and decreases the expression of KLF5	causes B-cell self-reactivity and autoantibody production	PBMCs from SLE patients and healthy controls	(98)
	miR-7	↑	negatively regulates the PTEN expression and down-regulates activation of PI3K/AKT signaling	promotes B cell differentiation into plasmablasts/plasma cells and spontaneous germinal center (GC) formation	MRL lpr/lpr lupus mice and their PBMCs	(35–37)
T cell	miR-21	↑	targets RASGRP1 to diminish Ras-MAPK pathway signaling and inhibit DNMT1 expression	contributes to DNA hypomethylation and T cell hyperactivity	SLE patients, lupus-prone MRL/lpr mice and healthy human PBMCs	(51–53)
			decreases expression level of PDCD4 to regulate IL-10 and CD40L	contributes to aberrant T cell phenotype	PBMCs from SLE patients and healthy controls
	miR-148a	↑	targets DNMT1 to regulate CD70 and LFA-1	contributes to DNA hypomethylation and T cell hyperactivity	SLE patients, lupus-prone MRL/lpr mice and healthy human PBMCs	(51)
	miR-126	↑	targets DNMT1 to induce demethylation and up-regulate CD70 and CD11a	contributes to DNA hypomethylation and T cell hyperactivity	PBMCs from SLE patients and healthy controls	(55, 99)
	miR-29b	↑	targets Sp1 to negatively regulate DNMT1 and increases the expression of CD70 and CD11a gene	contributes to DNA hypomethylation and T cell hyperactivity	PBMCs from SLE patients and healthy controls	(56)
	miR-145	↓	targets STAT-1 mRNA and ehances its expression level	associates with lupus nephritis significantly	PBMCs from SLE patients and healthy controls	(59)
	miR-224	↑	targets API5 mRNA and decreases its expression level	accelerates T cell activation-induced cell death in Jurkat cells
	miR-142-5p	↓	targets SLAM associated protein (SAP)	T cell activation and B cell hyperresponsiveness	PBMCs from SLE patients and healthy controls	(57)
	miR-142-3p	↓	targets SLAM family (IL-10 and CD84)	T cell activation and B cell hyperresponsiveness
immune tolerance	miR-21	↑	regulates FOXP3 expression positively	negatively regulates Treg cell development	umbilical cord blood mononuclear cells (UCBMC)	(68)
	miR-142-3p	↑	reduces the level of intracellular cAMP by inhibiting AC9 production	limits the suppressor function of Treg cells	splenocytes from naive BALB/c mice	(70)
	miR-31	↑	targets Gprc5a, Ppp6C and Foxp3	negatively regulates Treg cell generation and differentiation	PBMCs from murine and SLE patient	(68, 69)
	miR-17	↓	targets TGFβRII and CREB1	inhibits iTreg differentiation and facilitates effector T-cell responses	mice and PBMCs from SLE patients	(71, 72)
	miR-142-5p	↓	enhances Pde3b transcription and reduces the level of intracellular cAMP	key determinant of Treg function and peripheral immune tolerance	spleen and peripheral lymph nodes cells from mice	(58)
	miR-34a	↑	targets and attenuates the expression of Foxp3 gene	inhibits Treg cell differentiation and disrupts Treg/Th17 balance	PBMCs from murine and SLE patient	(65–67)
	miR-125a	↓	insufficiently targets and increases the expression of STAT3, Ifng, Il13	labilizes the immunoregulatory capacity of Treg cells	mice, SLE patient and their PBMCs	(63, 64)
	miR-15a	↑	activating the apoptotic pathway of the B-10 subset	weaken suppress effects of B-10 cells on SLE and other inflammatory diseases	Female (NZB × NZW)F1 or B/W mice	(46)
	miR-155	↑	inhibiting CD1d expression in B cells	impair the tolerance of NKT cells	Female C57BL/6J and MRL/lpr lupus-prone mice	(75)
inflammatory chemokine	miR-146a	↓	impairs negative regulation of multiple components expression in the type I IFN pathway, including IRAK1, TRAF6, IRF-5 and STAT-1	directly activates downstream of type I IFN	C57BL/6 mice, HEK293 cells	(90, 91)
	miR-125a	↓	increases KLF13 gene expression and hence RANTES expression	regulates inflammatory chemokines production and contribute to organ inflammation	PBMCs from SLE patients and healthy controls	(95)
	miR-181b	↓	directly regulates AID and IFN-α mRNAs	impairs negative regulation to IFN-α	PBMCs from SLE patients and healthy controls	(93)
	miR-410	↓	impairs negative regulation to transcription activity of STAT3	increases the expression levels of IL-10	PBLs from SLE patients and healthy controls	(100)
	miR-302d	↓	increases IRF9 gene expression and enhances ISG expression	negatively correlates with IFN score	PBMCs from SLE patients and healthy controls	(101)
	miR-31	↑	targets serine/threonine kinase 40	promotes NF-κB signaling to enhance inflammatory cytokine production.	PBMCs and splenocytes in MRL/lpr mice	(102)
	miR-98	↓	impairs targeting gene IL-6	promotes STAT3-mediated cell proliferation and inflammatory cytokine production	PBMCs from SLE patients and healthy controls	(96)
	miR-654	↓	inhibits MIF expression by binding to MIF mRNA	selectively suppresses the phosphorylation of ERK and AKT, reduces downstream inflammatory cytokine production	PBMCs from SLE patients and healthy controls	(103)