title: Vasoactive intestinal peptide maintains the nonpathogenic profile of human th17-polarized cells.
abstract: The cytokine microenvironment modulates CD4 T cell differentiation causing the shift of naïve CD4 T cells into different cell subsets. This process is also regulated by modulators such as vasoactive intestinal peptide (VIP), a neuropeptide with known immunomodulatory properties on CD4 T cells that exert this action through specific receptors, vasoactive intestinal peptide receptor (VPAC)1 and VPAC2. Our results show that the pattern of VIP receptors expression ratio is modified during Th17 differentiation. In this report, we evaluate the capacity of VIP to modulate naïve human cells into Th17 cells in vitro by analyzing their functional phenotype. The presence of VIP maintains the nonpathogenic profile of Th17-polarized cells, increases the proliferation rate, and decreases their Th1 potential. VIP induces the upregulation of the STAT3 gene interaction with the VPAC1 receptor during the onset of Th17 differentiation. Moreover, RAR-related orphan receptor C (RORC), RAR-related orphan receptor A (RORA), and interleukin (IL)-17A genes are upregulated in the presence of VIP through interaction with VPAC1 and VPAC2 receptors. Interestingly, VIP induces the expression of the IL-23R gene through interaction with the VPAC2 receptor during the expansion phase. This is the first report that describes the differentiation of naïve human T cells to Th17-polarized cells in the presence of VIP and demonstrates how this differentiation regulates the expression of the VIP receptors.
authors.affiliation: Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, 28040, Madrid, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Jimeno
authors.forename: Javier
authors.initials: J
authors.lastname: Leceta
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Irene
authors.initials: I
authors.lastname: Gutiérrez-Cañas
authors.forename: Mar
authors.initials: M
authors.lastname: Carrión
authors.forename: Selene
authors.initials: S
authors.lastname: Pérez-García
authors.forename: Marina
authors.initials: M
authors.lastname: Garín
authors.forename: Mario
authors.initials: M
authors.lastname: Mellado
authors.forename: Rosa P
authors.initials: RP
authors.lastname: Gomariz
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Juarranz
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010641:Phenotype; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: C515500:IL23R protein, human; D020381:Interleukin-17; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539738:RORA protein, human; C539900:RORC protein, human; D018123:Receptors, Interleukin; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014660:Vasoactive Intestinal Peptide