HLA-B27 does not trigger gut inflammation through the unfolded protein response

HLA-B27 does not trigger gut inflammation through the unfolded protein response hfabryova Fri, 09/06/2024 - 14:08 May 29, 2024 BASIC NIAMS IRP Robert A. Colbert, M.D., Ph.D. Pediatric Translational Research Branch Description Spondyloarthritis (SpA) is an inflammatory disease that affects the gastrointestinal tract, skeleton, and eyes. HLA-B27 is a major risk gene for SpA, but the underlying mechanisms are unclear. One hypothesis is that HLA-B27 promotes SpA through misfolding-induced endoplasmic reticulum (ER) stress that in turn upregulates IL-23 expression via the transcription factor CHOP. In this study, the researchers knocked out CHOP expression in an animal model of HLA-B27 -associated SpA. Despite reduced IL-23 production, gut inflammation did not improve, indicating that the gut disease did not occur as a result of ER stress-induced IL-23 production. What is exciting about this article? This work demonstrates that HLA-B27 -induced ER stress does not cause gut disease in SpA, which is an important advancement in the field to turn researchers’ attention to other pathways that may link HLA-B27 and SpA pathogenesis Grant support ZIA AR041184 Genetics and Genomics Immunology Molecular Biology and Biochemistry Light Imaging Section CHOP-mediated IL-23 overexpression does not drive colitis in experimental spondyloarthritis. Navid F, Gill T, Fones L, Allbritton-King JD, Zhou K, Shen I, Van Doorn J, LiCausi F, Cougnoux A, Randazzo D, Brooks SR, Colbert RA Sci Rep. 2024 May 29; 14 (1). doi: 10.1038/s41598-024-62940-0 PMID: 38811719 Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.