Paradoxical Activation of Entheseal Myeloid Cells by JAK1 and Tyk2 Inhibitors via Interleukin-10 Antagonism.

ABSTRACT:

Objective

JAK inhibition (JAKi) is effective in seronegative spondyloarthropathy (SpA) spectrum disorders, but Tyk2 inhibition failed in SpA spectrum ulcerative colitis, and tofacitinib showed minimal benefit in Crohn disease, which highlights the complex role for JAK/STAT signaling in different inflammatory processes. In this study, we investigated whether JAKi might paradoxically activate entheseal innate immunity and aimed to identify the key regulatory cytokines involved in this process.

Methods

Spinal entheseal tissue was activated with Toll-like receptor (TLR) agonists, including TLR4 and interleukin-1 (IL-1) family proteins, and entheseal T cells were activated with anti-CD3/anti-CD28 with IL-23/IL-1β. JAKi via upadacitinib (JAK1/JAK2), deucravacitinib (Tyk2), and rit

SUBMITTER: Giryes S 

PROVIDER: S-EPMC12479184 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature