Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse

Takeshita, Kenjiro; Yamasaki, Tsutomu; Akira, Shizuo; Gantner, Florian; Bacon, Kevin B.

doi:10.1093/intimm/dxh073

Cited by 104 publications

(109 citation statements)

References 48 publications

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“…To determine how CGRP augments the FITC-induced CHS, we studied the regulatory effect of CGRP on T cells in vivo. It has been reported that FITC-induced CHS involves response to Th2-mediated inflammation (26,27) and that IL-4 is essential for this response (27). Consistent with this report, we observed that the FITC-induced CHS response was remarkably suppressed in IL-4-deficient mice (data not shown); therefore, IL-4 appears to play a critical role in FITC-induced CHS.…”

Section: Cgrp Regulates the Fitc-induced Chs Response Via Regulation supporting

confidence: 90%

Calcitonin Gene-Related Peptide Is an Important Regulator of Cutaneous Immunity: Effect on Dendritic Cell and T Cell Functions

Mikami

Matsushita

Kato

et al. 2011

The Journal of Immunology

114

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Some cutaneous inflammations are induced by percutaneous exposure to foreign Ags, and many chemical mediators regulate this inflammation process. One of these mediators, calcitonin gene-related peptide (CGRP), is a neuropeptide released from nerve endings in the skin. CGRP binds to its receptors composed of receptor activity-modifying protein 1 and calcitonin receptor-like receptor to modulate immune cell function. We show that CGRP regulates skin inflammation under physiological conditions, using contact hypersensitivity (CHS) models of receptor activity-modifying protein 1–deficient mice. CGRP has different functions in CHS responses mediated by Th1 or Th2 cells; it inhibits Th1-type CHS, such as 2,4,6-trinitrochlorobenzene–induced CHS, but promotes Th2-type CHS, such as FITC-induced CHS. CGRP inhibits the migration of Langerin+ dermal dendritic cells to the lymph nodes in 2,4,6-trinitrochlorobenzene–induced CHS, and upregulates IL-4 production of T cells in the draining lymph nodes in FITC-CHS. These findings suggest that CGRP regulates several types of CHS reactions under physiological conditions and plays an important role in cutaneous immunity.

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Section: Cgrp Regulates the Fitc-induced Chs Response Via Regulation supporting

confidence: 90%

Calcitonin Gene-Related Peptide Is an Important Regulator of Cutaneous Immunity: Effect on Dendritic Cell and T Cell Functions

Mikami

Matsushita

Kato

et al. 2011

The Journal of Immunology

114

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“…One of small chemical haptens is dinitrofluorobenzene (DNFB), which is associated with the activation of Th1 cells. Upon challenging the skin with DNFB in mice sensitized with DNFB, DNFB-specific T cells are recruited to the skin and produce Th1 cytokines, including IFN-g and IL-2 after challenge, indicating that Th1 cells are important in DNFB-induced CHS response (3). In contrast, previous studies have shown that FITC-induced CHS is Th2 dominant (3)(4)(5)(6).…”

mentioning

confidence: 95%

“…Upon challenging the skin with DNFB in mice sensitized with DNFB, DNFB-specific T cells are recruited to the skin and produce Th1 cytokines, including IFN-g and IL-2 after challenge, indicating that Th1 cells are important in DNFB-induced CHS response (3). In contrast, previous studies have shown that FITC-induced CHS is Th2 dominant (3)(4)(5)(6). When FITC was used as a hapten, Th2-like response was observed with an IL-4/IFN-g ratio of 25, whereas more IFN-g than IL-4-secreting cells were found in draining lymph nodes from DNFB-sensitized mice with an IL-4/IFN-g ratio of 0.026 (4).…”

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confidence: 99%

CXCR3 Deficiency Prolongs Th1-Type Contact Hypersensitivity

Suga

Sugaya

Miyagaki

et al. 2013

The Journal of Immunology

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Sensitization and challenge using dinitrofluorobenzene (DNFB) induce contact hypersensitivity (CHS) with Th1 cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. In this study, we attempted to determine the role of CXCR3, a chemokine receptor, in Th1- and Th2-type CHS induced by DNFB or FITC using CXCR3-deficient (CXCR3−/−) mice. Ear swelling was prolonged after DNFB challenge in CXCR3−/− mice, which was accompanied by increased Th1 cytokines and decreased TGF-β and IL-10 expression at a late time point of CHS, whereas there was no significant difference between wild-type and CXCR3−/− mice in FITC-induced CHS. In Th1-type CHS, the number of regulatory T cells (Tregs) was decreased in the challenged ear of CXCR3−/− mice compared with that of wild-type mice, suggesting that CXCR3 would be important in migration of Tregs into the site of inflammation. Moreover, we examined the characteristics of CXCR3+ Tregs both in vitro and in vivo, revealing that CXCR3+ Tregs expressed high levels of TGF-β and IL-10 as well as IFN-γ compared with CXCR3− Tregs. When CXCR3−/− mice were injected with CXCR3+ Tregs, the prolonged ear swelling induced by DNFB was normalized. Taken together, our results suggest that CXCR3+ Tregs play a key role for quenching Th1-type CHS.

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“…From an immunologic perspective, CHS can be considered as a prototype of T-cell-mediated delayed-type hypersensitivity and is a reliable in vivo approach to follow the whole process of immune responses to some haptens where CD4 ϩ T cells are thought to play a pivotal role. 51,52 One mechanism that may account for defective MHC-II-restricted stimulation of T cells in vivo by Ag-loaded ICSBP Ϫ/Ϫ BM-DCs may stem from a defective ability of these cells to migrate from the injection site to the draining LN. This view is based on the observations that ICSBP Ϫ/Ϫ BM-DCs express low levels of CCR7 as well as impaired chemotactic response to the CCR7 ligands Mip-3␤ and 6CKine.…”

mentioning

confidence: 99%

ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells

Mattei

Schiavoni

Borghi

et al. 2006

Blood

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IntroductionDendritic cells (DCs) are the most powerful antigen-presenting cells (APCs), with unique features in initiating antigen (Ag)-specific immune responses, activating both naive CD4 ϩ and CD8 ϩ T lymphocytes. 1 To do so, DCs undergo a series of developmental changes in a process known as "maturation." Immature DCs are endowed with potent ability to capture Ags but are inefficient at presenting the processed Ags on their MHC class II (MHC-II) molecules, and thus are poor T-cell stimulators. Upon contact with microbial products or inflammatory cytokines, DCs are induced to mature and become highly efficient at presenting Ags and activating T cells while exhibiting reduced capacity for uptake and processing of newly encountered antigens. 2 Immature DCs are tuned to sample their environment and to capture any foreign particle. To accomplish this task, DCs use at least 2 mechanisms to internalize soluble proteins, fluid-phase macropinocytosis or receptor-mediated endocytosis by members of different receptor families. 3 The most prominent member of these membrane-bound proteins is the mannose receptor (MR). The MR acts as a pattern recognition molecule that enables efficient capture of mannosylated or fucosylated antigens, like dextran (DX), and is the main effector of receptor-mediated endocytosis. [4][5][6] In this regard, MRmediated uptake of Ags has been shown to potently enhance MHC-II-restricted Ag presentation in both human and mouse DCs. 7,8 In mouse spleen, distinct DC subtypes, including CD8␣ ϩ and CD8␣ Ϫ DCs, can be identified with diverse localization, ontogeny, and nature of immune response induced, but with a common ability to capture, process, and present soluble antigens. 9 Lymphoid organ-resident DCs have been generally considered as mature DCs based on high-level expression of costimulatory molecules as well as for their exceptional ability to stimulate both allogeneic T cells and Ag-specific naive T cells. 9,10 However, a number of reports have shown that spleen DC (s-DCs) can efficiently endocytose Ags, both in vitro and in vivo, suggesting that these cells may also exhibit features of immature DCs. [11][12][13][14][15] A recent study has clarified this controversy by showing that most subsets of lymphoid organ DCs, including CD8␣ ϩ and CD8␣ Ϫ s-DCs, are phenotypically and functionally immature in the steady state and are induced to mature only upon stimulation in vitro or in vivo. 16,17 This immature feature of s-DCs is particularly relevant for the maintenance of peripheral tolerance and allows DCs to promptly capture blood-circulating antigens and to mature in situ. 18 Interferon consensus sequence-binding protein (ICSBP), also known as interferon regulatory factor 8 (IRF-8), is a transcription factor that plays a prominent role in myeloid cell development as well as in the immune response to various infectious agents. 19,20 We and others have recently demonstrated that ICSBP is critically required for the normal development of defined DC populations. ICSBP Ϫ/Ϫ mice lack plasmacytoid DCs...

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Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse

Cited by 104 publications

References 48 publications

Calcitonin Gene-Related Peptide Is an Important Regulator of Cutaneous Immunity: Effect on Dendritic Cell and T Cell Functions

Calcitonin Gene-Related Peptide Is an Important Regulator of Cutaneous Immunity: Effect on Dendritic Cell and T Cell Functions

CXCR3 Deficiency Prolongs Th1-Type Contact Hypersensitivity

ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells

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