The Role of Sirtuin-1 in Immune Response and Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a potentially fatal multisystem inflammatory chronic disorder, the etiology and pathogenesis of which remain unclear. The loss of immune tolerance in SLE patients contributes to the production of autoantibodies that attack multiple organs and tissues, such as the skin, joints, and kidneys. Immune cells play important roles in the occurrence and progression of SLE through amplified immune responses. Sirtuin-1 (SIRT1), an NAD+-dependent histone deacetylase, has been shown to be a pivotal regulator in various physiological processes, including cell differentiation, apoptosis, metabolism, aging, and immune responses, via modulation of different signaling pathways, such as the nuclear factor κ-light-chain-enhancer of activated B cells and activator protein 1 pathways. Recent studies have provided evidence that SIRT1 could be a regulatory element in the immune system, whose altered functions are likely relevant to SLE development. This review aims to illustrate the functions of SIRT1 in different types of immune cells and the potential roles of SIRT1 in the SLE pathogenesis and its therapeutic perspectives.

Pinolenic acid exhibits Anti-inflammatory and Anti-atherogenic effects in Peripheral blood-derived Monocytes from patients with Rheumatoid Arthritis

“…SIRT1 can inhibit NF-κB pathway directly by itself or indirectly via forkhead family of transcription factors (FoxO) 16,18 . SIRT1 deacetylase was initially shown to deacetylate RelA/p65 at lysine 310 residue, which leads to reduced NF-κB transcriptional activity [19][20][21] . Substrates of SIRT1 are particularly abundant and include NF-κB RelA/p65, AP-1 family transcription factor c-Jun, and c-Myc.…”

Sirtuins are crucial regulators of T cell metabolism and functions

“…Most studies on Sirt1 have indicated that decreased Sirt1 expression or activity contributes to the enhancement of T cell activation, thereby leading to the occurrence of autoimmune diseases 58 . The immunoregulatory function of Sirt1 is dependent on the cell types and specific substrates that are targeted within the immune response.…”

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases

“…SLE, an incurable autoimmune disease, is due to inappropriate immune responses to nucleic acids containing cellular particles from the innate and adaptive immune system ( Qiu et al, 2021 ). The deposition of autoantibodies in kidney, skin, and lung is a characteristic of SLE ( Bialas et al, 2017 ).…”