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- W2045402079 abstract "Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. Methods The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin, an intercalating agent which causes DNA strand breaks. Lung fibrosis was evaluated in Baff deficient mice and in wild-type mice after neutralization of BAFF with BAFF-R-Ig. Lung cells from bleomycin-treated mice were collected at day 7, labeled with anti-CD115, anti-CD3, anti-CD19 and anti-Gr1 antibodies and sorted by FACS for evaluation of BAFF mRNA expression by qPCR. BAFF was quantified in bronchoalveolar lavage fluid (BALF) of controls and patients with IPF. Results We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1 + neutrophils as an important source of BAFF upon BLM induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1β levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1β- and IL-17A-dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3 + T cells from murine fibrotic lungs ex vivo . Finally, we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Conclusion The present data, demonstrating a critical role of BAFF by amplifying the IL-17A effect in experimental lung fibrosis, together with increased BAFF levels in the airways of patients with IPF, suggest that BAFF might be a therapeutic target of IPF." @default.
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- W2045402079 date "2015-03-01" @default.
- W2045402079 modified "2023-10-17" @default.
- W2045402079 title "B-cell activating factor regulates IL-1β- and IL-17A-mediated pulmonary fibrosis in mice" @default.
- W2045402079 doi "https://doi.org/10.1016/j.rmr.2015.02.021" @default.
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