The role of innate lymphoid cells in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a connective tissue disorder that affects various body systems. Both the innate and adaptive immunity contribute to the onset and progression of SLE. The main mechanism of SLE is an excessive immune response of immune cells to autoantigens, which leads to systemic inflammation and inflammation-induced organ damage. Notably, a subset of innate immune cells known as innate lymphoid cells (ILCs) has recently emerged. ILCs are pivotal in the early stages of infection; participate in immune responses, inflammation, and tissue repair; and regulate the immune function of the body by resisting pathogens and regulating autoimmune inflammation and metabolic homeostasis. Thus, ILCs dysfunction can lead to autoimmune diseases. This review discusses the maturation of ILCs, the potential mechanisms by which ILCs exacerbate SLE pathogenesis, and their contributions to organ inflammatory deterioration in SLE.

Therapeutic landscape in systemic lupus erythematosus: mtDNA activation of the cGAS-STING pathway.

Mitochondrial DNA (mtDNA) serves as a pivotal immune stimulus in the immune response. During stress, mitochondria release mtDNA into the cytoplasm, where it is recognized by the cytoplasmic DNA receptor cGAS. This activation initiates the cGAS-STING-IRF3 pathway, culminating in an inflammatory response. The cGAS-STING pathway has emerged as a critical mediator of inflammatory responses in microbial infections, stress, autoimmune diseases, chronic illnesses, and tissue injuries. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by connective tissue involvement across various bodily systems. Its hallmark is the production of numerous autoantibodies, which prompt the immune system to target and damage the body's own tissues, resulting in organ and tissue damage. Increasing evidence implicates the cGAS-STING pathway as a significant contributor to SLE pathogenesis. This article aims to explore the role of the mtDNA-triggered cGAS-STING pathway and its mechanisms in SLE, with the goal of providing novel insights for clinical interventions.

sNASP Mutation Aggravates to the TLR4-Mediated Inflammation in SLE by TAK1 Pathway.

Genetic factors play an important role in the pathogenesis of systemic lupus erythematosus (SLE), and abnormal Toll-like receptor (TLR) signaling pathways are closely related to the onset of SLE. In previous studies, we found that the mutant somatic nuclear autoantigenic sperm protein (sNASP) gene in the mouse lupus susceptibility locus Sle2 can promote the development of lupus model mice, but the mechanism is still unclear. Here, we stimulated mouse peritoneal macrophages with different concentrations of lipopolysaccharide. The results showed that sNASP gene mutations can promote the response of the TLR4-TAK1 signaling pathway but have no significant effect on the TLR4-TBK1 signaling pathway. sNASP mutations enhanced TLR4-mediated nuclear factor-κ-gene binding and mitogen-activated protein kinase activation and IL-6, tumor necrosis factor secretion in murine peritoneal macrophages. Collectively, our study revealed the impact of sNASP gene mutation on the sensitivity of TLR4 receptors in mouse peritoneal macrophages and shed light on potential mechanisms underlying inflammation in autoimmune diseases.