Yin, HongenKalra, LovikaLai, ZhennanDiniz, Maria Cambraia GuimaroAber, LaurenWarner, Blake M.Michael, DrewZhang, NanCabrera-Perez, JavierKarim, ArifSwaim, William D.Afione, SandraVoigt, AlexandriaNguyen, Cuong Q.Yu, Paul B.Bloch , Donald B.Chiorini, John A.2022-10-312022-10-312020-02-19Yin, H., Kalra, L., Lai, Z. et al. Inhibition of bone morphogenetic protein 6 receptors ameliorates Sjögren’s syndrome in mice. Sci Rep 10, 2967 (2020). https://doi.org/10.1038/s41598-020-59443-zhttps://doi.org/10.1038/s41598-020-59443-zhttp://hdl.handle.net/11603/26242Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease, with only palliative treatments available. Recent work has suggested that increased bone morphogenetic protein 6 (BMP6) expression could alter cell signaling in the salivary gland (SG) and result in the associated salivary hypofunction. We examined the prevalence of elevated BMP6 expression in a large cohort of pSS patients and tested the therapeutic efcacy of BMP signaling inhibitors in two pSS animal models. Increased BMP6 expression was found in the SGs of 54% of pSS patients, and this increased expression was correlated with low unstimulated whole saliva fow rate. In mouse models of SS, inhibition of BMP6 signaling reduced phosphorylation of SMAD1/5/8 in the mouse submandibular glands, and led to a recovery of SG function and a decrease in infammatory markers in the mice. The recovery of SG function after inhibition of BMP6 signaling suggests cellular plasticity within the salivary gland and a possibility for therapeutic intervention that can reverse the loss of function in pSS.13 pagesen-USThis work was written as part of one of the author's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.Public Domain Mark 1.0http://creativecommons.org/publicdomain/mark/1.0/Inhibition of bone morphogenetic protein 6 receptors ameliorates Sjögren’s syndrome in miceText