#Anti-Rat CD3 SAFIRE Purified ; #Anti-Rat CD28 SAFIRE Purified ; #05113-25; #10313-25 ;
Sci Signal. 2024 Feb 27;17(825):eadh1178.
Hao Cai 1, Jianhua Zhang 1, Hua Xu 1, Weiwei Sun 1, Weijie Wu 1, Chen Dong 2, Ping Zhou 3, Chengbin Xue 4, Yunyi Nan 1, Yingchen Ni 1, Xinyuan Wu 1, Zhifeng Gu 2, Minhao Chen 1, Youhua Wang 1
Affiliations expand
- PMID: 38412254
- DOI: 10.1126/scisignal.adh1178
Abstract
Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A4 (LTA4), were increased in CD4+ T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission. Knockdown or pharmacological inhibition of ALOX5 suppressed CD4+ T cell pyroptosis and improved symptoms in two rodent models of RA. Mechanistically, the increase in ALOX5 activity in RA CD4+ T cells enhanced the production of the LTA4 derivative LTB4, which stimulated Ca2+ influx through ORAI3 channels, leading to the activation of NLRP3 inflammasomes and pyroptosis. Our findings reveal a role for ALOX5 in RA and provide a molecular basis for further exploring the clinical utility of ALOX5 inhibition in RA and for using ALOX5 as a biomarker to distinguish active disease and remission in RA.