The pathogenic Th profile of human activated memory Th cells in early rheumatoid arthritis can be modulated by VIP



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Jimeno Lumeras, Rebeca Gema and Pérez Gomáriz, Rosa Mª and Garín, Marina and Gutiérrez Cañas, Irene and González Álvaro, Isidoro and Carrión Caballo, Mar and Galindo, María and Leceta Martínez, Javier and Juarranz Moratilla, Yasmina (2015) The pathogenic Th profile of human activated memory Th cells in early rheumatoid arthritis can be modulated by VIP. Journal of Molecular Medicine, 93 (4). pp. 457-467. ISSN 0946-2716, 1432-1440 (ESSN)

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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.

Item Type:Article
Uncontrolled Keywords:Rheumatoid arthritis, Th17, Th1, Vasoactive intestinal peptide, VPAC receptors
Subjects:Medical sciences > Medicine > Rheumatology
Medical sciences > Biology > Molecular biology
Medical sciences > Biology > Neurosciences
ID Code:29563
Deposited On:15 Apr 2015 08:31
Last Modified:08 Mar 2017 09:46

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