Knockdown of TRIM22 regulates the expression of NF-κB/NLRP3 and alleviates inflammation and renal injury in mice with lupus nephritis.

Abstract

Lupus nephritis (LN) is a common and clinically challenging complication of the systemic lupus erythematosus (SLE), but effective treatments remain imperative. Tripartite Motif Containing 22 (TRIM22) is a protein involved in various cellular processes, such as cell growth and inflammatory responses. However, the role and mechanism of TRIM22 in LN are still unclear. The aim of this study was to reveal the role of TRIM22 in LN and uncover the potential mechanisms. We discovered that TRIM22 is notably upregulated in renal tissues from patients with LN. Functionally, the knockdown of TRIM22 in lupus-prone MRL/lpr mice results in significant alleviation of LN symptoms, characterized by reduced proteinuria and improved renal function, as indicated by the lower serum levels of blood urea nitrogen and creatinine. Additionally, the intervention markedly decreases the deposition of immune complexes in the kidneys, further supporting the therapeutic potential of targeting TRIM22. Mechanically, the depletion of TRIM22 inhibits the NF-κB/NLRP3 pathway in mice with LN, but collectively, the knockdown of TRIM22 alleviates inflammation and renal injury in mice with LN via the NF-κB/NLRP3 axis.