biostudies-literatureUnknown21(2)Chen KLComplement's role in the pathology of rheumatoid arthritis and pulmonary hypertension (PH) is not fully understood. We aimed to determine whether complement deficiency is protective against joint and lung disease using the tumor necrosis factor-transgenic (TNF-Tg) mouse model characterized by chronic inflammatory-erosive arthritis and PH. TNF-Tg synovium and lungs were analyzed with bulk and single-cell RNA-sequencing. TNF-Tg mice were crossed with complement component 3 knockout (C3KO) and factor B knockout (fBKO) mice to quantify disease. Knee histology was scored, CD45 + Ly6C-C5aR1 + cells were quantified by flow cytometry, mid-hindpaw bone volumes were determined with micro-computed tomography, and lung disease was quantified with histology and right heart catheterization. TNF-Tg mice PloS onee0340677https://www.ebi.ac.uk/biostudies/studies/S-EPMC12875489biostudies-literatureMixed effects of complement in a chronic murine model of inflammatory erosive arthritis and pulmonary vascular disease.PMC12875489Duemmel SXu QChen KLNuzzo MWang GKenney HMRahimi HChristof MKorman BfalseMixed effects of complement in a chronic murine model of inflammatory erosive arthritis and pulmonary vascular disease.Complement's role in the pathology of rheumatoid arthritis and pulmonary hypertension (PH) is not fully understood. We aimed to determine whether complement deficiency is protective against joint and lung disease using the tumor necrosis factor-transgenic (TNF-Tg) mouse model characterized by chronic inflammatory-erosive arthritis and PH. TNF-Tg synovium and lungs were analyzed with bulk and single-cell RNA-sequencing. TNF-Tg mice were crossed with complement component 3 knockout (C3KO) and factor B knockout (fBKO) mice to quantify disease. Knee histology was scored, CD45 + Ly6C-C5aR1 + cells were quantified by flow cytometry, mid-hindpaw bone volumes were determined with micro-computed tomography, and lung disease was quantified with histology and right heart catheterization. TNF-Tg mice 2026-01-01T00:00:00Z20262026-07-05T03:13:11.942Z2026-07-05T03:08:40.489ZS-EPMC128754894164280410.1371/journal.pone.0340677