Tumor necrosis factor‑α in systemic lupus erythematosus: Structure, function and therapeutic implications (Review)

Abstract

Tumor necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine that contributes to the pathophysiology of several autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus (SLE). The specific role of TNF-α in autoimmunity is not yet fully understood however, partially, in a complex disease such as SLE. Through the engagement of the TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), both the two variants, soluble and transmembrane TNF-α, can exert multiple biological effects according to different settings. They can either function as immune regulators, impacting B-, T-and dendritic cell activity, modulating the autoimmune response, or as pro-inflammatory mediators, regulating the induction and maintenance of inflammatory processes in SLE. The present study reviews the dual role of TNF-α, focusing on the different effects that TNF-α may have on the pathogenesis of SLE. In addition, the efficacy and safety of anti-TNF-α therapies in preclinical and clinical trials SLE are discussed.

Loss of Gut Barrier Integrity In Lupus

“…For example, IL-13 and CXCL10 can modulate the movement of gut epithelial cells to expel parasites to avoid parasitic infection ( 79 ). Proinflammatory cytokines TNF- α , IL-1β and IFN-γ, all of which have been implicated in SLE pathogenesis ( 80 – 82 ), suppress the expression of tight junction proteins, alter the arrangement of tight junctions, and modulate the actin cytoskeleton in intestinal epithelial cells, resulting in a compromised gut barrier ( 83 , 84 ). Furthermore, IL-1β and IFN-γ exert their functions on tight junctions through the activation of the NF-κB pathway ( 85 , 86 ).…”

Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis

“… 67 , 68 Besides, TNF-α could act as a pro-inflammatory mediator, regulating the generation and maintenance of inflammation. 69 IL-6 increased TJ permeability by activating the c-jun N-terminal kinase pathway. 70 IL-1β down-regulated the mRNA expression of Occludin, resulting in increased intestinal TJ permeability.…”

An interpretable machine learning pipeline based on transcriptomics predicts phenotypes of lupus patients

“…Whereas some studies have found that TNF expression is related to SLE susceptibility, others have found that TNF expression is protective against SLE. 43 Another recent study found that TNF was the best discriminator of SLE from CTL patients out of 26 biomarkers, and it positively correlated to SLEDAI. 44 Likewise, we found that the module of TNF induced genes was one of the best discriminators of both SLE from CTL and LN from CTL blood.…”