DNGR1-Cre-mediated Deletion of Tnfaip3/A20 in Conventional Dendritic Cells Induces Pulmonary Hypertension in Mice.

DNGR1-Cre-mediated Deletion of Tnfaip3/A20 in Conventional Dendritic Cells Induces Pulmonary Hypertension in Mice. Am J Respir Cell Mol Biol. 2020 Aug 05;: Authors: Koudstaal T, van Hulst JAC, Das T, Neys SFH, Merkus D, Bergen IM, de Raaf MA, Bogaard HJ, Boon L, van Loo G, Aerts JGJV, Boomars KA, Kool M, Hendriks RW Abstract Chronic perivascular inflammation is a prominent feature in the lungs of idiopathic pulmonary arterial hypertension (IPAH). Although the proportions of conventional dendritic cells (cDCs) and plasmacytoid DCs are increased in IPAH lungs, it remains unknown whether activated cDCs play a pathogenic role. The Tnfaip3 gene encodes the ubiquitin-binding protein A20, which is a negative regulator of NF-κB, critically involved in DC activation. Targeting of Tnfaip3/A20 in cDCs was achieved by Clec9a (DNGR1)-Cre-mediated excision of the Tnfaip3 gene in Tnfaip3DNGR1-KO mice. Mice were evaluated for signs of pulmonary hypertension (PH) using right heart catheterization, echocardiography and measurement of the Fulton index. Inflammation was assessed by immunohistochemistry and flow cytometry. Pulmonary cDCs and mo-DCs from 31-week-old Tnfaip3DNGR1-KO mice showed modulated expression of cell surface activation markers compared to Tnfaip3DNGR1-WT mice. Tnfaip3DNGR1-KO mice developed elevated right ventricular (RV) systolic pressure and RV hypertrophy. The lungs of these mice displayed increased vascular remodeling and periva...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research