RT Journal Article T1 Activation of Th lymphocytes alters pattern expression and cellular location of VIP receptors in healthy donors and early arthritis patients A1 Villanueva Romero, Raúl A1 Gutiérrez Cañas, Irene A1 Carrión Caballo, Mar A1 González Álvaro, Isidoro A1 Rodríguez Frade, José Miguel A1 Mellado, Mario A1 Martínez, Carmen A1 Gomáriz, Rosa P. A1 Juarranz Moratilla, Yasmina AB Vasoactive Intestinal Peptide (VIP) is an important immunomodulator of CD4+ cells in normal and pathological conditions, which exerts its anti-infammatory and immunomodulatory actions through VPAC receptors, VPAC1 and VPAC2. Only a decrease in the expression of VPAC1 mRNA on Th cells upon activation has been reported. Thus, the deepening in the knowledge of the behavior of these receptors may contribute to the design of new therapies based on their activation and/or blockade. In this study, we describe the expression pattern, cellular location and functional role of VIP receptors during the activation of human Th cells in healthy conditions and in early arthritis (EA). The protein expression pattern of VPAC1 did not change with the activation of Th lymphocytes, whereas VPAC2 was up-regulated. In resting cells, VPAC1 was located on the plasma membrane and nucleus, whereas it only appeared in the nucleus in activated cells. VPAC2 was always found in plasma membrane location. VIP receptors signaled through a PKA-dependent pathway in both conditions, and also by a PKAindependent pathway in activated cells. Both receptors exhibit a potent immunomodulatory capacity by controlling the pathogenic profle and the activation markers of Th cells. These results highlight a novel translational view in infammatory/autoimmune diseases. PB Nature Research SN ESSN: 2045-2322 YR 2019 FD 2019-05-14 LK https://hdl.handle.net/20.500.14352/13486 UL https://hdl.handle.net/20.500.14352/13486 LA eng NO Instituto de Salud Carlos III/FEDER NO RETICS DS Docta Complutense RD 1 sept 2024