title: Retinaldehyde dehydrogenase activity is triggered during allograft rejection and it drives Th1/Th17 cytokine production.
abstract: Retinoic acid (RA), a vitamin A metabolite, has been attributed to relevant functions in adaptive immunity. On T cells, the disruption on RA signaling alters both CD4+ and CD8+ T cells effector function. In this study, we evaluated the contribution of RA synthesis during the immune response using an in vivo skin transplantation model. Our data indicates that the frequency and number of cells containing an active retinaldehyde dehydrogenase (RALDH), a key enzyme for RA synthesis, is increased during skin transplant rejection. In addition, we found that the expression of the mRNA coding for the isoform RALDH2 is up-regulated on graft rejecting draining lymph nodes (dLNs) cells. Lastly, we observed that IFN-γ and IL-17 production by ex vivo re-stimulated dLNs cells is greatly increased during rejection, which it turns depends on RA synthesis, as shown in experiments using a specific RALDH inhibitor. Altogether, our data demonstrate that RA synthesis is incremented during the immune response against an allograft, and also indicates that the synthesis of RA is required for cytokine production by dLNs resident T cells.
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Morales
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Campos-Mora
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Tania
authors.initials: T
authors.lastname: Gajardo
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Javier
authors.initials: J
authors.lastname: Campos
authors.affiliation: Immune Regulation and Tolerance Research Group, Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile(1).
authors.forename: Juan C
authors.initials: JC
authors.lastname: Aguillón
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Electronic address: karina.p.lagos@gmail.com.
authors.forename: Karina
authors.initials: K
authors.lastname: Pino-Lagos
mesh_terms: D064591:Allografts / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004789:Enzyme Activation; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D051379:Mice; D023421:Models, Animal; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D016038:Skin Transplantation; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*; D014184:Transplantation, Homologous; D014212:Tretinoin / Q000378:metabolism
chemical_list: D016207:Cytokines; D014212:Tretinoin; D050697:Retinal Dehydrogenase
keywords: Rejection; Retinoic acid; Th1/Th17; Transplantation