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Human CD4+CD45RA+ T Cells Behavior after In Vitro Activation: Modulatory Role of Vasoactive Intestinal Peptide



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Villanueva Romero, Raúl and Cabrera Martín, Alicia and Álvarez Corrales, Emigdio and Carrión Caballo, Mar and Pérez García, Selene and Lamana, Amalia and Castro Vázquez, David and Martínez Mora, Carmen and Gomáriz, Rosa P. and Gutiérrez Cañas, Irene and Juarranz Moratilla, Yasmina (2022) Human CD4+CD45RA+ T Cells Behavior after In Vitro Activation: Modulatory Role of Vasoactive Intestinal Peptide. International Journal of Molecular Sciences, 23 (4). pp. 1-19. ISSN 1661-6596, ESSN: 1422-0067

[thumbnail of Villanueva-Romero, R. et al. Human CD4+CD45RA+ T Cells Behavior....pdf]
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Official URL: https://doi.org/10.3390/ijms23042346


Naїve CD4+ T cells, which suffer different polarizing signals during T cell receptor activation, are responsible for an adequate immune response. In this study, we aimed to evaluate the behavior of human CD4+CD45RA+ T cells after in vitro activation by anti-CD3/CD28 bead stimulation for 14 days. We also wanted to check the role of the VIP system during this process. The metabolic biomarker Glut1 was increased, pointing to an increase in glucose requirement whereas Hif-1α expression was higher in resting than in activated cells. Expression of Th1 markers increased at the beginning of activation, whereas Th17-associated biomarkers augmented after that, showing a pathogenic Th17 profile with a possible plasticity to Th17/1. Foxp3 mRNA expression augmented from day 4, but no parallel increases were observed in IL-10, IL-2, or TGFβ mRNA expression, meaning that these potential differentiated Treg could not be functional. Both VIP receptors were located on the plasma membrane, and expression of VPAC2 receptor increased significantly with respect to the VPAC1 receptor from day 4 of CD4+CD45RA+ T activation, pointing to a shift in VPAC receptors. VIP decreased IFNγ and IL-23R expression during the activation, suggesting a feasible modulation of Th17/1 plasticity and Th17 stabilization through both VPAC receptors. These novel results show that, without polarizing conditions, CD4+CD45RA+ T cells differentiate mainly to a pathogenic Th17 subset and an unpaired Treg subset after several days of activation. Moreover, they confirm the important immunomodulatory role of VIP, also on naїve Th cells, stressing the importance of this neuropeptide on lymphocyte responses in different pathological or non-pathological situations.

Item Type:Article
Uncontrolled Keywords:naїve Th cells; CD4+CD45RA+ cells; Vasoactive intestinal peptide; VPAC receptors
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Biology > Biochemistry
ID Code:73976
Deposited On:22 Jul 2022 07:19
Last Modified:03 Aug 2022 09:56

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