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.
Highlights
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of various autoantibodies and damage to multiple organ systems [1]
We demonstrated that RNASE2 mRNA was highly expressed in peripheral blood mononuclear cells (PBMCs) from SLE patients and correlated with disease activity, autoantibody levels as well as proportion of associated B cell subset (ABCs)
Elevated peripheral blood RNASE2 mRNA expression was validated by real-time PCR in 60 SLE patients, compared with 20 patients with rheumatoid arthritis (RA), 20 patients with primary Sjögren’s syndrome (SS) or 37 HC (Figure 1A and Supplementary Table 3)
Summary
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of various autoantibodies and damage to multiple organ systems [1]. It is widely recognized that B cell dysfunction plays a major role in the pathogenesis of lupus [2]. The age-associated B cell subset (ABCs) has been the focus of increasing interest over the last decade [3]. ABCs express myeloid markers CD11c and depend on T-box transcription factor (T-bet) for their generation, called CD11c+T-bet+ B cells [4]. ABC-like B cells have been detected in human SLE and animal models [5], and were associated with disease activity and specific. RNASE2 Modulates Lupus Monocytes autoantibody profiles [6]. The molecular pathways that promote the expansion of ABC population in SLE patients is still largely unknown
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