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.
引用
收藏
页码:6501 / 6507
页数:7
相关论文
共 34 条
[1]   Tissue-tropic effector T cells: generation and targeting opportunities [J].
Agace, William W. .
NATURE REVIEWS IMMUNOLOGY, 2006, 6 (09) :682-692
[2]   'Educated' dendritic cells act as messengers from memory to naive T helper cells [J].
Alpan, O ;
Bachelder, E ;
Isil, E ;
Arnheiter, H ;
Matzinger, P .
NATURE IMMUNOLOGY, 2004, 5 (06) :615-622
[3]   Alcohol-induced gastritis prevents oral tolerance induction in mice [J].
Andrade, M. C. ;
Menezes, J. S. ;
Cassali, G. D. ;
Martins-Filho, O. A. ;
Cara, D. C. ;
Faria, A. M. C. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2006, 146 (02) :312-322
[4]   Essential role for CD103 in the T cell-mediated regulation of experimental colitis [J].
Annacker, O ;
Coombes, JL ;
Malmstrom, V ;
Uhlig, HH ;
Bourne, T ;
Johansson-Lindbom, B ;
Agace, WW ;
Parker, CM ;
Powrie, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (08) :1051-1061
[5]   ALPHA-4-BETA-7-INTEGRIN MEDIATES LYMPHOCYTE BINDING TO THE MUCOSAL VASCULAR ADDRESSIN MADCAM-1 [J].
BERLIN, C ;
BERG, EL ;
BRISKIN, MJ ;
ANDREW, DP ;
KILSHAW, PJ ;
HOLZMANN, B ;
WEISSMAN, IL ;
HAMANN, A ;
BUTCHER, EC .
CELL, 1993, 74 (01) :185-195
[6]   Lymphocyte homing and homeostasis [J].
Butcher, EC ;
Picker, LJ .
SCIENCE, 1996, 272 (5258) :60-66
[7]   Rapid acquisition of tissue-specific homing phenotypes by CD4+ T cells activated in cutaneous or mucosal lmphoid tissues [J].
Campbell, DJ ;
Butcher, EC .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (01) :135-141
[8]   The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells [J].
Campbell, JJ ;
Haraldsen, G ;
Pan, J ;
Rottman, J ;
Qin, S ;
Ponath, P ;
Andrew, DP ;
Warnke, R ;
Ruffing, N ;
Kassam, N ;
Wu, L ;
Butcher, EC .
NATURE, 1999, 400 (6746) :776-780
[9]   Dendritic cell immunization route determines CD8+ T cell trafficking to inflamed skin:: Role for tissue microenvironment and dendritic cells in establishment of T cell-homing subsets [J].
Dudda, JC ;
Simon, JC ;
Martin, S .
JOURNAL OF IMMUNOLOGY, 2004, 172 (02) :857-863
[10]   Dendritic cells from Peyer's patch and spleen induce different T helper cell responses [J].
Everson, MP ;
Lemak, DG ;
McDuffie, DS ;
Koopman, WJ ;
McGhee, JR ;
Beagley, KW .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1998, 18 (02) :103-115