Ciccia Francesco, McGonagle Dennis, Thomas Ranjeny, Marzo-Ortega Helena, Martin David A, Yndestad Arne, Volkov Mikhail
Dipartimento di Medicina di Precisione, Università della Campania L. Vanvitelli, Naples, Italy.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, The Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
Front Immunol. 2025 Mar 4;16:1488357. doi: 10.3389/fimmu.2025.1488357. eCollection 2025.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that predominantly affects the sacroiliac joints and spine. Tumor necrosis factor (TNF) and interleukin (IL)-17A are key cytokines in disease pathogenesis and are established axSpA treatment targets. Recently, axSpA treatment options have been complemented by Janus kinase inhibitors (JAKi), which inhibit various cytokines without directly impacting TNF or IL-17 signaling. The effect of JAKi on axSpA remains under investigation: besides a JAK2-mediated (and potentially tyrosine kinase 2 [TYK2]-mediated) effect on the IL-23/IL-17 axis, emerging evidence suggests γδ T cells, type 3 innate lymphoid cells, and mucosa-associated invariant T cells, which are dependent on IL-7 and/or IL-15 and thus on JAK1, are strongly inhibited by JAKi used to treat axSpA. This review summarizes potential effects of JAKi on axSpA and shows evidence from pre-clinical/clinical studies. Greater understanding of the mechanisms of action of available treatments may improve knowledge of axSpA and pave the road for future therapies.
轴性脊柱关节炎（axSpA）是一种主要影响骶髂关节和脊柱的慢性炎症性疾病。肿瘤坏死因子（TNF）和白细胞介素（IL）-17A是疾病发病机制中的关键细胞因子，也是已确立的axSpA治疗靶点。最近，Janus激酶抑制剂（JAKi）补充了axSpA的治疗选择，JAKi可抑制多种细胞因子，而不直接影响TNF或IL-17信号传导。JAKi对axSpA的作用仍在研究中：除了对IL-23/IL-17轴有JAK2介导（可能还有酪氨酸激酶2 [TYK2]介导）的作用外，新出现的证据表明，依赖IL-7和/或IL-15因而依赖JAK1的γδ T细胞、3型固有淋巴细胞和黏膜相关恒定T细胞，会被用于治疗axSpA的JAKi强烈抑制。这篇综述总结了JAKi对axSpA的潜在作用，并展示了临床前/临床研究的证据。对现有治疗作用机制的更深入了解可能会增进对axSpA的认识，并为未来的治疗铺平道路。
