Advances in systemic lupus erythematosus pathogenesis via mTOR signaling pathway

Abstract

Objective: To elucidate the role of mTOR signaling pathway in the pathogenesis of systemic lupus erythematosus (SLE) and possible applications of the inhibitors in treatment of SLE.

Methods: PubMed, OVID, Embase, Web of Science, and Cochrane library databases were searched up to April 2019 with combined keywords of 'systemic lupus erythematosus', 'mammalian target of rapamycin (mTOR)' and 'signaling pathway'. Studies reporting mTOR and pathogenesis of SLE were included. Given the heterogeneity in study design, different quality assessment tools were applied appropriately.

Results: We retrieved 329 articles, among which 69 were included in the review. The available evidences have shown that mTOR signaling pathway is closely associated with the proliferation and differentiation of immune cells, the secretion of inflammatory cytokines, the abnormalities of autophagy and oxidative stress, and plays an important role in the pathogenesis of SLE. The efficacy and safety of mTOR inhibitors in SLE clinical trials have been initially confirmed.

Conclusions: mTOR signaling pathway is closely related to the pathogenesis of SLE. The improved understanding of immunoregulation and the completion of more clinical trials is expected to define mTOR-targeted therapeutic intervention as a new target for precision medicine of treatment of SLE. More extensive and future research with larger trial populations is required to determine its efficacy and tolerability.

Keywords: Autophagy; Immune regulation; Oxidative stress; Rapamycin; Systemic lupus erythematosus; mTOR signaling pathway.