共 34 条
Imprinting of CCR9 on CD4 T cells requires IL-4 signaling on mesenteric lymph node dendritic cells
被引:53
作者:
Elgueta, Raul
[2
,3
]
Sepulveda, Fernando E.
[2
,3
]
Vilches, Felipe
[2
]
Vargas, Leonardo
[2
,3
]
Mora, J. Rodrigo
[1
,4
]
Bono, Maria Rosa
[2
,3
]
Rosemblatt, Mario
[1
,2
,3
,5
]
机构:
[1] Fdn Ciencia Vida, Santiago, Chile
[2] Univ Chile, Fac Ciencias, Dept Biol, Santiago, Chile
[3] Millennium Inst Fundamental & Appl Biol, Santiago, Chile
[4] Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA
[5] Univ Andres Bello, Santiago, Chile
关键词:
D O I:
10.4049/jimmunol.180.10.6501
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
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.
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页码:6501 / 6507
页数:7
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