S1P1 receptor signaling overrides retention mediated by Gαi-coupled receptors to promote T cell egress

被引:345
作者
Pham, Trung H. M. [1 ]
Okada, Takaharu [1 ,2 ]
Matioubian, Mehrdad [1 ]
Lo, Charles G. [1 ]
Cyster, Jason G. [1 ]
机构
[1] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
关键词
D O I
10.1016/j.immuni.2007.11.017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The mechanism by which sphingosine-1-phosphate receptor-1 (S1P(1)) acts to promote lymphocyte egress from lymphoid organs is not defined. Here, we showed that CCR7-deficient T cells left lymph nodes more rapidly than wild-type cells did, whereas CCR7-overexpressing cells were retained for longer. After treatment with FTY720, an agonist that causes down-modulation of lymphocyte S1P(1), CCR7-deficient T cells were less effectively retained than wild-type T cells. Moreover, treatment with pertussis toxin to inactivate signaling via G alpha(i)-protein-coupled receptors restored egress competence to S1P(1)-deficient lymphocytes. We also found that T cell accumulation in lymph node cortical sinusoids required intrinsic S1P(1) expression and was antagonized by CCR7. These findings suggest a model where S1P(1) acts in the lymphocyte to promote lymph node egress by overcoming retention signals mediated by CCR7 and additional G alpha(i)-coupled receptors. Furthermore, by simultaneously upregulating S1P(1) and downregulating CCR7, T cells that have divided multiple times switch to a state favoring egress over retention.
引用
收藏
页码:122 / 133
页数:12
相关论文
共 44 条
[31]   CC chemokine receptor 7 contributes to Gi-dependent T cell motility in the lymph node [J].
Okada, Takaharu ;
Cyster, Jason G. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (05) :2973-2978
[32]   B cell migration and interactions in the early phase of antibody responses [J].
Okada, Takaharu ;
Cyster, Jason G. .
CURRENT OPINION IN IMMUNOLOGY, 2006, 18 (03) :278-285
[33]   Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate [J].
Pappu, Rajita ;
Schwab, Susan R. ;
Cornelissen, Ivo ;
Pereira, Joao P. ;
Regard, Jean B. ;
Xu, Ying ;
Camerer, Eric ;
Zheng, Yao-Wu ;
Huang, Yong ;
Cyster, Jason G. ;
Coughlin, Shaun R. .
SCIENCE, 2007, 316 (5822) :295-298
[34]   Rapid plasma membrane-endosomal trafficking of the lymph node sinus and high endothelial venule scavenger receptor/homing receptor stabilin-1 (Feel-1/CLEVER-1) [J].
Prevo, R ;
Banerji, S ;
Ni, J ;
Jackson, DG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (50) :52580-52592
[35]   Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position [J].
Reif, K ;
Ekland, EH ;
Ohl, L ;
Nakano, H ;
Lipp, M ;
Förster, R ;
Cyster, JG .
NATURE, 2002, 416 (6876) :94-99
[36]   Rapid induction of medullary thymocyte phenotypic maturation and egress inhibition by nanomolar sphingosine 1-phosphate receptor agonist [J].
Rosen, H ;
Alfonso, C ;
Surh, CD ;
McHeyzer-Williams, MG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (19) :10907-10912
[37]   Tipping the gatekeeper: S1P regulation of endothelial barrier function [J].
Rosen, Hugh ;
Sanna, M. Germana ;
Cahalan, Stuart M. ;
Gonzalez-Cabrera, Pedro J. .
TRENDS IN IMMUNOLOGY, 2007, 28 (03) :102-107
[38]   Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo [J].
Sanna, M. Germana ;
Wang, Sheng-Kai ;
Gonzalez-Cabrera, Pedro J. ;
Don, Anthony ;
Marsolais, David ;
Matheu, Melanie P. ;
Wei, Sindy H. ;
Parker, Ian ;
Jo, Euijung ;
Cheng, Wei-Chieh ;
Cahalan, Michael D. ;
Wong, Chi-Huey ;
Rosen, Hugh .
NATURE CHEMICAL BIOLOGY, 2006, 2 (08) :434-441
[39]   CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells [J].
Schneider, Martin A. ;
Meingassner, Josef G. ;
Lipp, Martin ;
Moore, Henrietta D. ;
Rot, Antal .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (04) :735-745
[40]   Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients [J].
Schwab, SR ;
Pereira, JP ;
Matloubian, M ;
Xu, Y ;
Huang, Y ;
Cyster, JG .
SCIENCE, 2005, 309 (5741) :1735-1739