A Role for CCR9 in T Lymphocyte Development and Migration

Uehara, Shotaro; Grinberg, Alexander; Farber, Joshua M.; Love, Paul E.

doi:10.4049/jimmunol.168.6.2811

Cited by 293 publications

(326 citation statements)

References 49 publications

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“…CCR9 + γδ T lymphocytes, which are present in the thymus, peripheral lymph nodes, and spleen, have been shown to be attracted by CCL25 in vitro [6,11,15]. Our data demonstrate that CCL25 drives the in vivo migration of CCR9 + γδ T lymphocytes during allergic inflammation (or when directly injected), by using an experimental model of murine pleurisy.…”

Section: Discussionmentioning

confidence: 59%

CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction

Costa¹,

Bornstein²,

Candéa³

et al. 2012

Eur J Immunol

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Herein, we provide evidence that during allergic inflammation, CCL25 induces the selective migration of IL-17 + γδ T cells mediated by α 4 β 7 integrin. Intrapleural injection of CCL25 into ovalbumin (OVA)-immunized C57BL/6 mice triggered the accumulation of γδ T lymphocytes expressing CCR9 (CCL25 receptor) and α 4 β 7 integrin in the pleura, but failed to attract αβ T lymphocytes. CCL25 attracted CCR6 + γδ T cells producing IL-17 (but not IFN-γ or IL-4). OVA challenge triggered increased production of CCL25 followed by the accumulation of CCR9 + , α 4 β 7 + , and CCR6 + /IL-17 + γδ T cells into the pleural cavities of OVA-immunized mice, which was inhibited by the in vivo neutralization of CCL25. The in vivo blockade of α 4 β 7 integrin also inhibited the migration of IL-17 + γδ T lymphocytes (but not of αβ T lymphocytes) into mouse pleura after OVA challenge, suggesting that the CCL25/α 4 β 7 integrin pathway is selective for γδ T cells. In addition, α 4 β 7 integrin blockade impaired the in vitro transmigration of γδ T cells across endothelium (which expresses α 4 β 7 ligands VCAM-1 and MadCAM-1), which was induced by CCL25 and by cell-free pleural washes recovered from OVA-challenged mice. Our results reveal that during an allergic reaction, CCL25 drives IL-17 + γδ T-cell mobilization to inflamed tissue via α 4 β 7 integrin and modulates IL-17 levels. Keywords: Adhesion molecules IntroductionLymphocytes bearing the γδ T-cell receptor (TCR) comprise a minor T-lymphocyte subset in blood and secondary lymphoid tissues and are preferentially localized in epithelial and mucosal tissues [1,2]. This unique subset of lymphocytes can provide rapid tissue-specific immune responses, without the requirement of antiCorrespondence: Dr. Carmen Penido e-mail: cpenido@far.fiocruz.br gen presentation or clonal expansion, and is able to produce a large repertory of Th1-, Th2-, and Th17-associated cytokines [2][3][4][5][6]. These characteristics make γδ T cells a crucial first line of defense during infection, tissue damage, or stress.γδ T cells have been shown to migrate into the airways during allergic inflammation highly controlled by a chemotactic gradient of chemokines produced in tissue [5,[7][8][9][10][11]. We have previously demonstrated that allergen-induced γδ T-cell accumulation is * These authors contributed equally to this work.www.eji-journal.eu Eur. J. Immunol. 2012. 42: 1250-1260 Immunomodulation 1251 paralleled with a marked production of chemokines in the tissue, including CCL25/TECK [11]. CCL25 is mostly described as a homeostatic chemokine that plays a major role in T-cell development in the thymus and in intraepithelial lymphocytes (IELs) homing into small intestine mucosa [12]. Recent data have provided evidence that CCL25 production increases during inflammatory processes that take place at nonmucosal tissues, such as autoimmune arthritis, atherosclerosis, and allergy [11,13,14]. Moreover, we and others have shown that γδ T lymphocytes migrate in vitro toward CCL25, via its counterpart receptor CCR9 [11,...

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Section: Discussionmentioning

confidence: 59%

CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction

Costa¹,

Bornstein²,

Candéa³

et al. 2012

Eur J Immunol

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“…However, we and others have shown that the apparent lack of thymic phenotype for CCR9 Ϫ/Ϫ mice is misleading (6,12), which is probably also the case for CCL25 Ϫ/Ϫ mice. This is because a very important component of normal lymphocyte trafficking, i.e., competition (26) for limited microenvironmental niches between CCR9 ϩ and CCR9 Ϫ thymocyte populations, is missing in CCR9 Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 99%

“…The vast majority of small-intestinal T and B lymphocytes express high levels of CCR9 (3,13). Some T cell subsets are significantly reduced within the intestinal epithelium of CCR9-deficient mice (12,16), suggesting that CCR9 is necessary for steady-state intestinal T cell development and/or gut tropism. Additionally, adoptive transfer assays demonstrate that CCR9 ϩ/ϩ lymphocytes are more efficient than CCR9 Ϫ/Ϫ lymphocytes at homing to the small intestine (17).…”

Section: Impaired Accumulation Of Antigen-specific Cd8 Lymphocytes Inmentioning

confidence: 99%

“…In the thymus, CCL25-CCR9 interactions appear to play an important role in the migration of early T cells into the cortex from the subcapsular zone after successful TCR␤ gene rearrangement (4 -7). CCR9 may also play an earlier role in thymic development, either by directly controlling thymic colonization (8 -10) or by participating in thymic precursor development within the bone marrow (BM) 3 (6,11,12).…”

Section: Impaired Accumulation Of Antigen-specific Cd8 Lymphocytes Inmentioning

confidence: 99%

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Impaired Accumulation of Antigen-Specific CD8 Lymphocytes in Chemokine CCL25-Deficient Intestinal Epithelium and Lamina Propria

Wurbel

Malissen

Guy‐Grand

et al. 2007

The Journal of Immunology

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CCL25 and CCR9 constitute a chemokine/receptor pair involved in T cell development and in gut-associated immune responses. In this study, we generated CCL25−/− mice to answer questions that could not be addressed with existing CCR9−/− mice. Similar phenotypes were observed for both CCL25−/− and CCR9−/− mice, consistent with the notion that CCL25 and CCR9 interact with each other exclusively. We assessed the requirement for CCL25 in generating CCR9high CD8 intestinal memory-phenotype T cells and the subsequent accumulation of these cells within effector sites. TCR-transgenic naive CD8 T cells were transferred into wild-type or CCL25-deficient hosts. Oral sensitization with Ag allowed these naive donor cells to efficiently differentiate into CCR9high memory-phenotype cells within the mesenteric lymph nodes of wild-type hosts. This differentiation event occurred with equal efficiency in the MLN of CCL25-deficient hosts, demonstrating that CCL25 is not required to induce the CCR9high memory phenotype in vivo. However, we found that CCL25 deficiency severely impaired the Ag-dependent accumulation of donor-derived CD8 T cells within both lamina propria and epithelium of the small intestine. Thus, although CCL25 is not necessary for generating memory-phenotype CD8 T cells with “gut-homing” properties, this chemokine is indispensable for their trafficking to the small intestine.

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“…Recently, a homophilic molecule expressed both on lymphocytes and epithelial cells, Ep-CAM, has been identified in the pig as a possible contributor to IEL retention within the epithelium [47]. In mice, the chemokine receptor CCR9 seems to partake in directing lymphocyte migration to the epithelium [94]. In general, chemokines and their respective receptors have been identified as key regulators of lymphocyte migration in mice and humans.…”

Section: Regulation Of Lymphocyte Migrationmentioning

confidence: 99%

Lymphocyte migration studies

Bimczok

Rothkötter

2006

Vet. Res.

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-For maintenance of immunity and tolerance, the organs and tissues of the organism are connected by migrating lymphoid cells. Understanding lymphocyte migration is essential for many disorders and diseases -especially in the mucosa-lined organs. Detailed analyses of migrating lymphocytes have been performed in many species, especially in laboratory animals. However, important experiments in lymphocyte migration have been carried out in large animals, for example sheep, cattle and pigs. These species allow experimental procedures like in situ-organ labelling, lymphocyte retransfusion studies or lymph vessel cannulations. Such studies have made an important contribution to the understanding of the overall principles of lymphocyte migration especially in the mucosal immune system. Major results on the specific migration of naïve and memory T cells through lymphoid organs, the re-distribution of γ/δ T cells in the intestinal immune system and the emigration of newly produced B cells from the ileal Peyer's patches have been obtained in large animals. Since there are growing numbers of markers for large animals, and molecular biology methods are available in these species, experiments in large animals will be an essential tool for the understanding of lymphocyte migration especially in mucosal organs.

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A Role for CCR9 in T Lymphocyte Development and Migration

Cited by 293 publications

References 49 publications

CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction

CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction

Impaired Accumulation of Antigen-Specific CD8 Lymphocytes in Chemokine CCL25-Deficient Intestinal Epithelium and Lamina Propria

Lymphocyte migration studies

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A Role for CCR9 in T Lymphocyte Development and Migration

Cited by 293 publications

References 49 publications

CCL25 induces α4β7 integrin‐dependent migration of IL‐17+γδ T lymphocytes during an allergic reaction

CCL25 induces α4β7 integrin‐dependent migration of IL‐17+γδ T lymphocytes during an allergic reaction

Impaired Accumulation of Antigen-Specific CD8 Lymphocytes in Chemokine CCL25-Deficient Intestinal Epithelium and Lamina Propria

Lymphocyte migration studies

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Product

Resources

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CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction

CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction