Identification of three distinct subsets of migrating dendritic cells from oral mucosa within the regional lymph nodes

Chalermsarp, Narumon; Azuma, Miyuki

doi:10.1111/j.1365-2567.2008.03031.x

Cited by 28 publications

(29 citation statements)

References 32 publications

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“…Similar to the results as shown in Fig. 4A (38,46,47). Dermal DCs cannot directly interact with KCs in the epidermis; however, GITR-mediated KC-derived cytokines may affect dermal DCs directly or indirectly (via LC-produced cytokines) and result in modulating migratory properties of dermal DCs.…”

Section: Discussionsupporting

confidence: 73%

The Glucocorticoid-Induced TNF Receptor-Related Protein (GITR)-GITR Ligand Pathway Acts As a Mediator of Cutaneous Dendritic Cell Migration and Promotes T Cell-Mediated Acquired Immunity

Kamimura

Iwai

Piao

et al. 2009

The Journal of Immunology

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Glucocorticoid-induced TNFR-related protein (GITR) has various roles in the activation of T cells and inflammation. In this study, we investigated the roles of the GITR-GITR ligand (GITRL) pathway in contact hypersensitivity (CH). Treatment with anti-GITRL mAb at sensitization inhibited CH responses. Depletion studies using an anti-CD25 or anti-PDCA-1 mAb revealed that regulatory T cells and plasmacytoid dendritic cells (DCs), known to express high levels of GITR and GITRL, respectively, were not apparently involved in GITRL-mediated CH responses. Treatment with/addition of anti-GITRL mAb in the experiments for hapten-specific T cell proliferation and IFN-γ production showed a minor contribution of the GITRL, which was weakly expressed on DCs in draining lymph nodes (dLNs). Interestingly, anti-GITRL mAb treatment inhibited the migration of cutaneous DCs to the dLNs. Epidermal keratinocytes (KCs) constitutively express GITR, whereas Langerhans cells (LCs) express higher levels of GITRL compared with DCs in dLNs. GITR ligation, by an anti-GITR mAb, in KCs promoted expression of multiple proinflammatory cytokines and blockade of GITRL-inhibited IL-1β and CCR7 expression in sensitized skin. These results suggest that the GITR-GITRL pathway promotes epidermal inflammatory cytokine production by KCs and LCs, resulting in migration of cutaneous DCs from the skin to the dLNs. This is the first report demonstrating the involvement of the GITR-GTRL pathway in interactions with KCs and LCs and the migration of DCs. Our findings provide important implications for understanding the molecular bases of KC-LC interactions and for developing new therapeutic strategies in skin disease.

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Section: Discussionsupporting

confidence: 73%

The Glucocorticoid-Induced TNF Receptor-Related Protein (GITR)-GITR Ligand Pathway Acts As a Mediator of Cutaneous Dendritic Cell Migration and Promotes T Cell-Mediated Acquired Immunity

Kamimura

Iwai

Piao

et al. 2009

The Journal of Immunology

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“…Cryostat sections (4-5 mm thick) were stained with anti-B7-H1 mAb (MIH5) as described previously (31). For TUNEL staining, cryostat sections were stained with Apoptosis in situ Detection Kit Wako (Wako).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Keratinocyte-Associated B7-H1 Directly Regulates Cutaneous Effector CD8+ T Cell Responses

Ritprajak

Hashiguchi

Tsushima

et al. 2010

The Journal of Immunology

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Keratinocytes (KCs) may play important roles for maintenance of peripheral tolerance in the upper layers of the skin. Coinhibitory signals mediated via the programmed death (PD)-1 and its ligand B7-H1 (PD-L1/CD274) are crucial for the downregulation of T cell immune responses and for the maintenance of peripheral tolerance. In this study, to investigate the role of KC-expressed B7-H1 in the regulation of T cell immune responses, we generated transgenic (tg) mice overexpressing B7-H1 under the control of keratin 14 (K14) promoter (K14-B7-H1 tg). K14-B7-H1 tg mice displayed impaired contact hypersensitivity (CH) responses to primary and secondary hapten challenges. The K14-B7-H1 tg mice did not exhibit substantial impairment of cutaneous dendritic cell migration after sensitization and of hapten-specific proliferation and IFN-γ production of CD4+ and CD8+ T cells in the draining lymph nodes, suggesting that overexpression of B7-H1 on KCs did not affect the induction phase of the CH response. The systemic or s.c. injection of hapten-sensitized T cells into the K14-B7-H1 tg mice did not efficiently induce the CH response. IFN-γ expression and apoptosis of KCs in the challenged ears were impaired in K14-B7-H1 tg mice. IFN-γ production by presensitized CD8+ T cells stimulated with hapten-pulsed KCs was markedly impaired for the KCs obtained from the K14-B7-H1 tg mice but was restored by the addition of an anti–B7-H1 mAb. These results suggest that KC-associated B7-H1 directly downregulates the effector function of CD8+ T cells by associating with PD-1 at local inflammatory sites and that it plays a role in peripheral T cell tolerance against exogenous Ags.

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“…Histology was assessed by 2 independent investigators. Cryostat sections were stained with anti-B7-H1 (MIH5) mAb, and enzymatic immunohistochemistry was performed as described previously (26).…”

Section: Histology and Immuohistochemistrymentioning

confidence: 99%

B7-H1 Overexpression Regulates Epithelial–Mesenchymal Transition and Accelerates Carcinogenesis in Skin

Cao

Zhang²,

Kamimura³

et al. 2011

Cancer Research

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B7-H1 (CD274) is a T-cell coinhibitory molecule that is also often induced on human carcinoma cells, where its expression has been implicated in immune escape. Under inflammatory conditions, B7-H1 is also inducible in normal epithelial cells but little is known about its involvement in conversion of normal cells to tumor cells. Here, we show that skin-specific expression of B7-H1 accelerates inflammatory carcinogenesis in a methylcholantrene (MCA)-induced model of squamous cell carcinoma (SCC). Inflammatory responses induced by MCA or phorbol ester TPA were clearly inhibited in B7-H1 transgenic mice (B7-H1tg mice). Antibody-mediated blockade of either B7-H1 or the related molecule PD-1 revealed that their ability to limit inflammation relied on ligand interactions made by B7-H1 or PD-1. Skin keratinocytes derived from B7-H1tg mice exhibited constitutive reduction of E-cadherin, and SCC induced in B7-H1tg mice also showed loss of E-cadherin along with elevated expression of the transcription factors Slug and Twist that drive epithelial-mesenchymal transition (EMT). Our results indicate that upregulation of B7-H1 in skin epithelial cells promotes EMT and accelerates carcinogenesis, revealing insights into the significance of B7-H1 overexpression on solid tumor cells and hinting at a close relationship between EMT and immune escape signaling pathways in cancer. Cancer Res; 71(4); 1235-43. Ó2010 AACR.

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Identification of three distinct subsets of migrating dendritic cells from oral mucosa within the regional lymph nodes

Cited by 28 publications

References 32 publications

The Glucocorticoid-Induced TNF Receptor-Related Protein (GITR)-GITR Ligand Pathway Acts As a Mediator of Cutaneous Dendritic Cell Migration and Promotes T Cell-Mediated Acquired Immunity

The Glucocorticoid-Induced TNF Receptor-Related Protein (GITR)-GITR Ligand Pathway Acts As a Mediator of Cutaneous Dendritic Cell Migration and Promotes T Cell-Mediated Acquired Immunity

Keratinocyte-Associated B7-H1 Directly Regulates Cutaneous Effector CD8+ T Cell Responses

B7-H1 Overexpression Regulates Epithelial–Mesenchymal Transition and Accelerates Carcinogenesis in Skin

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