MALAT1 is involved in type I IFNs-mediated systemic lupus erythematosus by up-regulating OAS2, OAS3, and OASL

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an aberrant activation of immune cells partly due to the dysfunction of cytokines such as type I interferons (IFNs). Long non-coding RNA MALAT1 has been found to play a pathogenic role in SLE; however, the underlying mechanisms are still poorly understood. Bioinformatics analysis showed the up-regulation of type I IFN downstream effectors OAS2, OAS3, and OASL (OAS-like) in CD4 + T cells, CD19 + B cells, and CD33 + myeloid cells in patients with active SLE compared to healthy participants. In this study, peripheral blood mononuclear cells (PBMCs), CD19 + B, and CD4 + T cells were isolated from active SLE patients and healthy participants. PCR was performed to quantify MALAT1, OAS2, OAS3, and OASL expression in immune cells. MALAT1, OAS2, OAS3, and OASL were knocked down in CD4 + T cells to investigate the regulatory effect of MALAT1 on the effectors and their involvement in type I IFNs-mediated inflammation. Results showed higher OAS2, OAS3, and OASL expression in active SLE patients. MALAT1 expression was positively correlated to OAS2, OAS3, and OASL expression in CD19 + B or CD4 + T cells. MALAT1 knockdown decreased OAS2, OAS3, and OASL expression. Treatment with IFN-a-2a increased the expression of TNF-a, IL-1b, and IFN-a in CD4 + T cells. However, knockdown of MALAT1, OAS2, OAS3, and OASL alone inhibited the effect of IFN-a-2a on TNF-a and IL-1b. This study suggested the involvement of MALAT1 in type I IFNs-mediated SLE by up-regulating OAS2, OAS3, and OASL.

Aberrant Non-Coding RNA Expression in Patients with Systemic Lupus Erythematosus: Consequences for Immune Dysfunctions and Tissue Damage

“…NONHSAT039491.2 was associated with lupus activity and the presence of anti-dsDNA, anti-RNP, and other neuropsychiatric manifestations. Gao et al [103] have found that MALTAT1 is involved in type 1 IFN-mediated SLE by up-regulating OAS2, OAS3, and OASL, confirming further the report by Ye et al [104] claiming that full high-throughput sequencing analysis of lncRNA expression profile in SLE-PBMCs could reveal a robust "IFN signature". A comprehensive review of ncRNA in SLE-CD4 + T cells with new insights into lupus pathogenesis has been published by Gao et al [105].…”

Interferon Lambda 3/4 (IFNλ3/4) rs12979860 Polymorphisms Is Not Associated With Susceptibility to Systemic Lupus Erythematosus, Although It Regulates OASL Expression in Patients With SLE

“…In light of this, OASL expression can be useful as a biomarker of SLE, as relative OASL mRNA expression levels are upregulated in active SLE patients and OASL may be a discriminant for systemic infection in SLE ( Ye et al, 2007 ). However, patients with active SLE who had renal disorders showed upregulated OASL in PBMCs and CD19 + B cells compared to that in patients without clinical manifestations ( Gao et al, 2020 ).…”

Characterization of Type I Interferon-Associated Chemokines and Cytokines in Lacrimal Glands of Nonobese Diabetic Mice

“…This process results in cell death as a means to prevent viral survival and spread. While the association of OAS family members with autoimmunity is not new [ 27 , 28 , 29 , 30 , 31 ], the specific mechanisms by which OAS family members may contribute to autoimmunity is not well-described. In an individual with defects in clearing apoptotic cells, an anti-viral response via OAS family members could conceivably provide increased antigen or ligand for innate immune receptors such as Toll-like receptor 7 (TLR7) or other pattern recognition receptors.…”