Epigenetic targets of Janus kinase inhibitors are linked to genetic risks of rheumatoid arthritis.

ABSTRACT:

Background

Current strategies that target cytokines (e.g., tumor necrosis factor (TNF)-α), or signaling molecules (e.g., Janus kinase (JAK)) have advanced the management for allergies and autoimmune diseases. Nevertheless, the molecular mechanism that underpins its clinical efficacy have largely remained elusive, especially in the local tissue environment. Here, we aimed to identify the genetic, epigenetic, and immunological targets of JAK inhibitors (JAKis), focusing on their effects on synovial fibroblasts (SFs), the major local effectors associated with destructive joint inflammation in rheumatoid arthritis (RA).

Methods

SFs were activated by cytokines related to inflammation in RA, and were treated with three types of JAKis or a TNF-α inhibitor (TNFi). Dynamic changes in

SUBMITTER: Tsuchiya H 

PROVIDER: S-EPMC11149281 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature