Potential Use of Janus Kinase Inhibitors in the Treatment of Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease with unclear pathogenesis. One characteristic of SLE is pro-inflammatory and anti-inflammatory cytokine imbalance. Janus kinase (JAK) is an intracellular non-receptor tyrosine kinase essential for many cytokine signaling pathways. Dysregulation of the JAK/signal transduction and transcriptional activator (STAT) pathway is an important process in SLE pathogenesis. Targeting JAK/STAT proteins can simultaneously block the functions of multiple cytokines. Current SLE treatment with non-specific corticosteroids and immunosuppressants can cause many adverse reactions. Therefore, treatments designed to control specific molecular targets for SLE are desirable. JAK inhibitors (JAKis) are a potential treatment for rheumatic diseases; however, the use of targeted signaling pathways to treat SLE remains a challenge, and its efficacy has not been determined. JAKis have shown positive results in reducing the use of glucocorticoids and/or non-specific immunosuppressants for SLE. JAKis are currently undergoing several clinical trials and expected to be the next stage in the treatment of SLE. Therefore, inhibition of the JAK/STAT pathway through JAKis may improve traditional treatment strategies for SLE.

JAK-STAT pathway activation compromises nephrocyte function in aDrosophilahigh-fat diet model of chronic kidney disease

“…Patients with this complication show activated JAK-STAT and elevated leptin, regulated by Sterol regulatory element bending transcription factor 1 (SREBF1) which is involved in lipogenesis (Hao et al, 2013). Already, phase 2/3 clinical trials are underway to study the efficacy of JAK inhibitors in treating lupus nephritis (Huo et al, 2023). Our data indicate a possible second pathway could contribute, by direct leptin stimulation of JAK-STAT caused by the dysregulated fat body, warranting further investigation.…”