EBI1-ligand chemokine (ELC) attracts a broad spectrum of lymphocytes: activated T cells strongly up-regulate CCR7 and efficiently migrate toward ELC

Yoshida, Ruriko; Nagira, Morio; Imai, Toshio; Baba, Masataka; Takagi, Shin; Tabira, Yoichi; Akagi, Junji; Nomiyama, Hisayuki; Yoshie, Osamu

doi:10.1093/intimm/10.7.901

Cited by 96 publications

(78 citation statements)

References 35 publications

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“…This cascade of events is required for extravasation of naive T cells into lymph node, a process that occurs constantly throughout life. The specific combination of ligands and receptors also is critical, because although neutrophils express L selectin (and can roll on lymph node venules), they do not express CCR7 and thus are not activated in this setting (34). Therefore, lymph nodes allow only a select population of lymphocytes to enter from blood.…”

Section: Discussionmentioning

confidence: 99%

Embryonic trafficking of γδ T cells to skin is dependent on E/P selectin ligands and CCR4

Jiang

Campbell

Kupper

2010

Proc. Natl. Acad. Sci. U.S.A.

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Dendritic epidermal T cells (DETC) express an invariant Vγ3/Vδ1 T-cell receptor, appear in fetal epidermis, and form a population of resident epidermal T cells. Their temporal development in the thymus has been studied extensively. However, little is known about the mechanisms involved in the embryonic trafficking of DETC from thymus to epidermis. We demonstrate that DETC in adult skin, as well as the DETC precursors in fetal thymus, express E and P selectin ligands (E-and P-lig). Mice deficient in α1,3 fucosyltransferases IV and VII (FTIV/VII) cannot synthesize the carbohydrate motifs that form key elements of these selectin ligands. The numbers of DETC in the epidermis of FTIV/VII −/− mice were dramatically reduced compared with normal mice. However, the development of DETC precursors in fetal thymus was identical in normal and FTIV/VII −/− mice, suggesting that the DETC precursors produced in FTIV/VII −/− mice could not traffic effectively to skin because they lack E-and P-lig. We tested this hypothesis by daily injection of blocking antibodies against E and P selectin into pregnant mice. Mice born from dams treated with anti-selectin antibodies, but not those born from dams treated with isotype control, had significantly diminished numbers of DETC. To test the role of chemokine receptors in DETC skin homing, we examined skin from CCR4 −/− and CCR10 −/− mice, respectively. DETC were significantly reduced in CCR4 −/− mice but were present at normal levels in CCR10 −/− mice. Our results present evidence for the crucial role of trafficking molecules in embryonic migration of DETC precursors to skin. central to host defense against pathogens, and bear T-cell receptors (TCR) that are heterodimers of either α and β or γ and δ TCR genes. T cells with γδ TCR are much less abundant than αβ TCR cells in the adult thymus, blood, and peripheral lymphoid organs but are more abundant in epithelial layers of tissues, such as skin, intestine, lung, and genitourinary tract (1-4). Murine dendritic epidermal T cells (DETC) are a unique population of γδ T cells that reside in murine epidermis. They have a dendritic morphology in situ and express a distinctive invariant Vγ3/Vδ1 TCR that recognizes a putative self-antigen expressed on the damaged, stressed, or transformed keratinocytes (5). In the past decade, significant advances have been made in understanding the roles of DETC in tissue homeostasis and wound healing (6-8). Recently, DETC were shown to contribute to the regression of cutaneous tumors through NKG2D ligation and to regulate autoimmune skin disease (9, 10). DETC also may be important mediators in bridging innate and adaptive immunity of skin through communication with keratinocytes and Langerhans cells (11).The thymus is a unique site that provides an inductive environment for T-lineage commitment and V(D)J recombination at the γδ and αβ TCR loci. Vγ3/Vδ1 T cells are the first TCR-bearing cells to arise in the fetal thymus and selectively home to the skin between embryonic day (ED) 16 and 18 (12, 13). It initially...

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Section: Discussionmentioning

confidence: 99%

Embryonic trafficking of γδ T cells to skin is dependent on E/P selectin ligands and CCR4

Jiang

Campbell

Kupper

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…To confirm that the HuT 78 cell line internalized and recycled in a manner similar to the CCR7 expressed in peripheral blood cells (44), we used FACS based internalization and receptor recycling assays. CCR7 is activated by two endogenous ligands, CCL19 and CCL21 (25,31,47). Initially, to identify an optimal concentration of ligand for our assays, we conducted a dose response ( Fig.…”

Section: Characterization Of Ccr7 Expression and Internalization In Hmentioning

confidence: 99%

Arrestin 3 Mediates Endocytosis of CCR7 following Ligation of CCL19 but Not CCL21

Byers

Calloway

Shannon

et al. 2008

The Journal of Immunology

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Internalization of ligand bound G protein-coupled receptors, an important cellular function that mediates receptor desensitization, takes place via distinct pathways, which are often unique for each receptor. The C-C chemokine receptor (CCR7) G protein-coupled receptor is expressed on naive T cells, dendritic cells, and NK cells and has two endogenous ligands, CCL19 and CCL21. Following binding of CCL21, 21 ± 4% of CCR7 is internalized in the HuT 78 human T cell lymphoma line, while 76 ± 8% of CCR7 is internalized upon binding to CCL19. To determine whether arrestins mediated differential internalization of CCR7/CCL19 vs CCR7/CCL21, we used small interfering RNA (siRNA) to knock down expression of arrestin 2 or arrestin 3 in HuT 78 cells. Independent of arrestin 2 or arrestin 3 expression, CCR7/CCL21 internalized. In contrast, following depletion of arrestin 3, CCR7/CCL19 failed to internalize. To examine the consequence of complete loss of both arrestin 2 and arrestin 3 on CCL19/CCR7 internalization, we examined CCR7 internalization in arrestin 2−/−/arrestin 3−/− murine embryonic fibroblasts. Only reconstitution with arrestin 3-GFP but not arrestin 2-GFP rescued internalization of CCR7/CCL19. Loss of arrestin 2 or arrestin 3 blocked migration to CCL19 but had no effect on migration to CCL21. Using immunofluorescence microscopy, we found that arrestins do not cluster at the membrane with CCR7 following ligand binding but cap with CCR7 during receptor internalization. These are the first studies that define a role for arrestin 3 in the internalization of a chemokine receptor following binding of one but not both endogenous ligands.

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“…It binds to the chemokine receptors CCR7 (13) and CCR11 (14). Murine CCL21 also binds to CXCR3 (15).…”

Section: Ectopic Expression Of the Murine Chemokines Ccl21a Andmentioning

confidence: 99%

Ectopic Expression of the Murine Chemokines CCL21a and CCL21b Induces the Formation of Lymph Node-Like Structures in Pancreas, But Not Skin, of Transgenic Mice

Chen¹,

Vassileva²,

Kinsley³

et al. 2002

The Journal of Immunology

182

155

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The CC chemokine CCL21 is a potent chemoattractant for lymphocytes and dendritic cells in vitro. In the murine genome there are multiple copies of CCL21 encoding two CCL21 proteins that differ from each other by one amino acid at position 65 (either a serine or leucine residue). In this report, we examine the expression pattern and biological activities of both forms of CCL21. We found that although both serine and leucine forms are expressed in most tissues examined, the former was the predominant form in lymphoid organs while the latter was predominantly expressed in nonlymphoid organs. When expressed in transgenic pancreas, both forms of CCL21 were capable of inducing the formation of lymph node-like structures composed primarily of T and B cells and a few dendritic cells. Induction of lymph node-like structures by these CCL21 proteins, however, could not be reproduced in every tissue. For instance, no lymphocyte recruitment or accumulation was observed when CCL21 was overexpressed in the skin. We conclude that both forms of CCL21 protein are biologically equivalent in promoting lymphocyte recruitment to the pancreas, and that their ability to induce the formation of lymph node-like structures is dependent on the tissues in which they are expressed.

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EBI1-ligand chemokine (ELC) attracts a broad spectrum of lymphocytes: activated T cells strongly up-regulate CCR7 and efficiently migrate toward ELC

Cited by 96 publications

References 35 publications

Embryonic trafficking of γδ T cells to skin is dependent on E/P selectin ligands and CCR4

Embryonic trafficking of γδ T cells to skin is dependent on E/P selectin ligands and CCR4

Arrestin 3 Mediates Endocytosis of CCR7 following Ligation of CCL19 but Not CCL21

Ectopic Expression of the Murine Chemokines CCL21a and CCL21b Induces the Formation of Lymph Node-Like Structures in Pancreas, But Not Skin, of Transgenic Mice

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