RNASE2 Mediates Age-Associated B Cell Expansion Through Monocyte Derived IL-10 in Patients With Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies. Ribonuclease A family member 2 (RNase2) is known to have antiviral activity and immunomodulatory function. Although RNASE2 level has been reported to be elevated in SLE patients based on mRNA microarray detection, its pathologic mechanism remains unclear. Here, we confirmed that RNASE2 was highly expressed in PBMCs from SLE patients and associated with the proportion of CD11c+T-bet+ B cells, a class of autoreactive B cells also known as age-associated B cells (ABCs). We showed that reduction of RNASE2 expression by small interfering RNA led to the decrease of ABCs in vitro, accompanied by total IgG and IL-10 reduction. In addition, we demonstrated that both RNASE2 and IL-10 in peripheral blood of lupus patients were mainly derived from monocytes. RNASE2 silencing in monocytes down-regulated IL-10 production and consequently reduced ABCs numbers in monocyte-B cell co-cultures, which could be restored by the addition of recombinant IL-10. Based on above findings, we concluded that RNASE2 might induce the production of ABCs via IL-10 secreted from monocytes, thus contributing to the pathogenesis of SLE.

RNase2 is a possible trigger of acute-on-chronic inflammation leading to mRNA vaccine-associated cardiac complication

“…RNASE2 encodes the ribonuclease RNase2, which has been known to be an endogenous Toll-like receptor 2 (TLR2) ligand that drives Th2 response. 8 Recently, RNase2 was also found to be an integral part of endosomal synthetic RNA sensing; RNase2 cooperates with RNase T2 to cleave RNA on either side of uridine to form TLR8 ligands. 9 Consistent with this recent report, we found heightened expression of TLR8, but not other TLRs, at pre-booster baseline and on day 4 post-booster vaccination ( Figures S2 D–S2M).…”

Identification of diagnostic biomarkers for idiopathic pulmonary hypertension with metabolic syndrome by bioinformatics and machine learning

“…This suggests that RNASE2 plays an important role in the immune system 29 . As an immune-related molecule, RNASE2 is a biomarker of various immune system diseases, including chronic myelogenous leukemia, systemic lupus erythematosus, rheumatoid arthritis, and multiple myeloma [30][31][32][33] . In terms of cancer, RNASE2 www.nature.com/scientificreports/ promotes the malignant progression of glioma through the PI3K/Akt signaling pathway 34 .…”

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

“…The altered expression of CX3CR1 [599], S100A12 [600], PF4 [601], MPO (myeloperoxidase) [602], RXFP1 [603], S100A8 [604], VEGFD (vascular endothelial growth factor D) [605], CXCL11 [606], IL1A [607], BPI (bactericidal permeability increasing protein) [608], SLC6A4 [609], CXCL10 [610], FCGR3B [611], S100A9 [612], IL1B [613], CXCR2 [614], CTNND2 [615], CD36 [616], PCSK9 [617], FGF2 [618], SHH (sonic hedgehog signaling molecule) [619], KL (klotho) [620], BMPR2 [621], TLR8 [622], GATA3 [623], CCR2 [624], TLR7 [625], CAV1 [626], TFPI (tissue factor pathway inhibitor) [627] and SPAG17 [628] have been identified in systemic sclerosis. A previous study found that CX3CR1 [629], S100A12 [630], MPO (myeloperoxidase) [631], CD5L [632], F11 [633], S100A8 [634], BPI (bactericidal permeability increasing protein) [635], AQP4 [636], MME (membrane metalloendopeptidase) [637], BDNF (brain derived neurotrophic factor) [638], CXCL10 [639], RNASE2 [640], FCGR3B [641], S100A9 [642], GPIHBP1 [643], AFF3 [644], APOH (apolipoprotein H) [645], FCN3 [646], PCSK9 [308], LILRA2 [647], APOA1 [648], LRRK2 [649], CD244 [650], TLR3 [651], TLR8 [652], GATA3 [653], CCR2 [654], IFIT3 [655], NEK7 [656], TLR7 [657], CAV1 [658], CR1 [659], TFPI (tissue factor pathway inhibitor) [660], GPER1 [661], SIGLEC14 [662], FOXJ1 [663], GABRP (gamma-aminobutyric acid type A receptor subunit pi) [664] and TSGA10 [665] are positively correlated with the severity of systemic lupus erythematosus, suggesting its potential as a biomarker ...…”