title: Effect of VIP on the balance between cytokines and master regulators of activated helper T cells.
abstract: CD4T helper cells are decisive in the struggle against pathogens and in maintaining immune homeostasis. Nevertheless, they also drive immune-mediated disease. Recently, emerging evidence suggests that seemingly committed Th cells possess plasticity and may convert into other types of effector cells. Vasoactive Intestinal Peptide (VIP) is an immunomodulator neuropeptide, which is able to promote or inhibit individually the differentiation or function of some T-helper subsets. We conducted ex vivo study with erythrocyte-depleted spleen cells from healthy mice to check the balance between cytokines and master regulators of different T-helper subsets. This neuropeptide adversely affected the differentiation and functionality phases of Th17 cells and had a negative influence on cytokines related to Th1 function, increasing Th17 cells over those of the Th1 cell subset. With respect to Th2 subsets, VIP augmented the interleukin (IL)-4/IL-9 mRNA ratio, and a negative correlation between IL-4 and IL-9 was observed in culture supernatants. VIP augmented Th2 relative to Th1 in cell subsets. VIP decreased the iTreg/Th17 balance. Regarding the induced T-regulatory (iTreg)/Th1 balance, VIP increased the presence of immunoregulatory cytokines in relation to IFNγ. Although additional studies are needed to clarify the role of VIP on the balance between cytokines and master regulators during T-helper differentiation, our data show that VIP reduces Th17/Th1 and Th1/Th2 ratios. However, the iTreg/Th17 ratio was differently counterbalanced, probably because of culture conditions. Finally, this is the first study showing that VIP also modulates Th2/Th9 and iTreg/Th1 ratios.
authors: Departamento de Biología Celular, Universidad Complutense de Madrid, Madrid, Spain.
authors: Rebeca
authors: R
authors: Jimeno
authors: Javier
authors: J
authors: Leceta
authors: Carmen
authors: C
authors: Martínez
authors: Irene
authors: I
authors: Gutiérrez-Cañas
authors: Selene
authors: S
authors: Pérez-García
authors: Mar
authors: M
authors: Carrión
authors: Rosa P
authors: RP
authors: Gomariz
authors: Yasmina
authors: Y
authors: Juarranz
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics; D016906:Interleukin-9 / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: D016906:Interleukin-9; D012333:RNA, Messenger; D015847:Interleukin-4; D014660:Vasoactive Intestinal Peptide; D007371:Interferon-gamma