Elgueta, RaulSepulveda, Fernando E.Vilches, FelipeVargas, LeonardoMora, J. RodrigoBono, Maria RosaRosemblatt, Mario2024-07-302024-07-302008-05-15JOURNAL OF IMMUNOLOGY, Volume 180, Issue 10, Page 6501-65070022-1767https://repositorio.unab.cl/handle/ria/58859INDEXACIÓN: WEB OF SCIENCE.It has recently been shown that IL-4 can educate dendritic cells (DC) to differentially affect T cell effector activity. In this study, we show that IL-4 can also act upon DC to instruct naive T cells to express the gut-associated homing receptor CCR9. Thus, effector T cells generated after coculture with mesenteric lymph node (MLN)-DC show a higher expression of CCR9 when activated in the presence of IL-4. In contrast, IL-4 had no effect on CCR9 expression when naive T cells were polyclonally activated in the absence of MLN-DC, suggesting that the effect of IL-4 on CCR9 expression passed through DC. Indeed, T cells activated by MLN-DC from IL-4R alpha(-/-) mice showed a much lower CCR9 expression and a greatly reduced migration to the small intestine than T cells activated by wild-type MLN-DC even in-the presence of IL-4. Consistent with the finding that the vitamin A metabolite retinoic acid (RA) induces gut-homing molecules on T cells, we further demonstrate that IL-4 up-regulated retinaldehyde dehydrogenase 2 mRNA on MLN-DC, a critical enzyme involved in the synthesis of RA. Moreover, LE135, a RA receptor antagonist, blocked the increased expression of CCR9 driven by IL-4-treated MLN-DC. Thus, besides the direct effect of RA on T cell gut tropism, our results show that the induction of a gut-homing phenotype on CD4(+) T cells is also influenced by the effect of IL-4 on gut-associated DC.enPEYERS PATCHINFLAMED SKINTISSUEGUTLYMPHOCYTESMEMORYLOCALIZATIONGENERATIONCHEMOKINESEXPRESSIONArtículo10.4049/jimmunol.180.10.6501