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


Journal of Clinical & Experimental Neuroimmunology

Author(s): Jimeno R, Gomariz RP, Garn M, GutirrezCaas I, Gonzlezlvaro I

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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 analyses were performed. An increase in CCR6(+)/RORC(+) cells and in RORC-proliferating cells and a decrease in T-bet-proliferating 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.

This article was published in J Mol Med (Berl) and referenced in Journal of Clinical & Experimental Neuroimmunology

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