Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells

Raul Elgueta, Fernando E. Sepulveda, Felipe Vilches, Leonardo Vargas, J. Rodrigo Mora, Maria Rosa Bono, Mario Rosemblatt

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50 Citations (Scopus)

Abstract

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-4Rα-/- 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 dehy-drogenase 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.

Original languageEnglish
Pages (from-to)6501-6507
Number of pages7
JournalJournal of Immunology
Volume180
Issue number10
DOIs
Publication statusPublished - 1 Jan 2008

ASJC Scopus subject areas

  • Immunology

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    Elgueta, R., Sepulveda, F. E., Vilches, F., Vargas, L., Mora, J. R., Bono, M. R., & Rosemblatt, M. (2008). Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells. Journal of Immunology, 180(10), 6501-6507. https://doi.org/10.4049/jimmunol.180.10.6501