NLRP12 Deficiency Enhances Tofacitinib Efficacy in DSS Colitis Via STAT1-M1 Polarization.

ABSTRACT: Tofacitinib, an oral pan-Janus kinase (JAK) inhibitor, induces rapid remission in ulcerative colitis (UC), but only ~60% of patients respond, highlighting the need for biomarkers to guide therapy. NLRP12, a NOD-like receptor, negatively regulates inflammation by restraining NF-κB signaling and modulating microbiota-host interactions. We hypothesized that NLRP12 deficiency skews macrophage polarization toward an M1-biased state dependent on JAK-STAT signaling, thereby enhancing responsiveness to JAK inhibition. Acute colitis was induced by Dextran Sodium Sulfate (DSS) in wild-type and Nlrp12^⁻/⁻ mice. Disease severity was assessed by body weight, disease activity index, colon length, and histopathology. Tofacitinib (10 mg/kg) was administered orally from day 3 to 7. Macrophage inf

SUBMITTER: Yi Y 

PROVIDER: S-EPMC12920396 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature