RT Journal Article T1 The pathogenic Th profile of human activated memory Th cells in early rheumatoid arthritis can be modulated byVIP A1 Jimeno Lumeras, Rebeca Gema A1 Pérez Gomáriz, Rosa María A1 Garín, Marina I. A1 Gutiérrez Cañas, Irene A1 González Álvaro, Isidoro A1 Carrión Caballo, Mar A1 Galindo, María A1 Leceta Martínez, Javier A1 Juarranz Moratilla, Yasmina AB Our aim is to study the behavior of memory Th cells (Th17, Th17/1, and Th1 profiles) from early rheumatoid arthritis (eRA) patients after their in vitro activation/expansion to provide information about its contribution to RA chronicity. Moreover, we analyzed the potential involvement of vasoactive intestinal peptide (VIP) as an endogenous healing mediator. CD4+CD45RO+ T cells from PBMCs of HD and eRA were activated/expanded in vitro in the presence/absence of VIP. FACS, ELISA, RT-PCR, and immunocytochemistry analyseswere performed. An increase in CCR6+/RORC+ cells and in RORC-proliferating cells and a decrease in T-betproliferating cells and T-bet+/RORC+ cells were shown in eRA. mRNA expression of IL-17, IL-2, RORC, RORA, STAT3, and Tbx21 and protein secretion of IL-17, IFNγ, and GM-CSF were higher in eRA. VIP decreased the mRNA expression of IL-22, IL-2, STAT3, Tbx21, IL-12Rβ2, IL-23R, and IL-21R in HD and it decreased IL-21, IL-2, and STAT3 in eRA. VIP decreased IL-22 and GM-CSF secretion and increased IL-9 secretion in HD and it decreased IL-21 secretion in eRA. VPAC2/VPAC1 ratio expression was increased in eRA. All in all, memory Th cells from eRA patients show a greater proportion of Th17 cells with a pathogenic Th17 and Th17/1 profile compared to HD. VIP is able to modulate the pathogenic profile, mostly in HD. Our results are promising for therapy in the early stages of RA because they suggest that targeting molecules involved in the pathogenic Th17, Th17/1, and Th1 phenotypes and targeting VIP receptors could have a therapeutic effect modulating these subsets. PB Springer SN 0946-2716, 1432-1440 (ESSN) YR 2015 FD 2015 LK https://hdl.handle.net/20.500.14352/33984 UL https://hdl.handle.net/20.500.14352/33984 LA eng NO Instituto de Salud Carlos III NO Comunidad de Madrid DS Docta Complutense RD 6 oct 2024