Activation Pattern of Langerhans Cells in the Afferent and Efferent Phases of Contact Hypersensitivity

Araki, M.; Imafuku, Shinichi; Furue, Masutaka; Shimada, Shinji; Tamaki, Kunihiko

doi:10.1038/sj.jidsp.5640202

Cited by 6 publications

(9 citation statements)

References 53 publications

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“…However, it has recently been demonstrated that LCs are at least partly also involved in the elicitation phase of allergic contact dermatitis, because ablation of LCs reduces the inflammatory response (24). It has also been verified that the LC density decreases significantly in the elicitation phase, and that this decrease can be prevented by tacrolimus and cyclosporine A (25), and this corresponds to our findings with tacrolimus, rapamycin, and cilomilast (4).…”

Section: Discussionsupporting

confidence: 91%

“…The results for systemically administered ASA were somewhat unexpected. As observed for cilomilast, tacrolimus cyclosporine A and rapamycin (4, 25), our concept was that a reduced migration of DCs is accompanied by a reduced inflammatory response (ear swelling). This was also the case with indomethacin and diflorasone diacetate in the present study.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Non‐steroidal and steroidal anti‐inflammatory drugs vary in their modulation of dendritic cell function in the elicitation phase of allergic contact dermatitis

Bäumer

Krekeler

Devries

et al. 2006

Experimental Dermatology

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The role of dendritic cells (DCs) in allergic contact dermatitis has been clearly demonstrated for the induction phase. However, the situation during the elicitation phase is very complex within a distinct inflammatory response. This study was performed to exploit DC migration in the elicitation phase in a mouse model of allergic contact dermatitis and to evaluate the effects of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) on DC migration through skin in the elicitation phase of allergic contact dermatitis. Topically and systemically administered acetylsalicylic acid (ASA) did not reduce the inflammatory response. However, systemically administered ASA significantly reduced the DC migration to the draining lymph node. In contrast, topically administered indomethacin reduced the inflammatory response, but had only minor effects on DC migration, whereas diflorasone diacetate reduced both inflammatory reaction and DC migration. Thus, NSAIDs may differ in their inhibitory action in immunological inflammation.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 91%

Non‐steroidal and steroidal anti‐inflammatory drugs vary in their modulation of dendritic cell function in the elicitation phase of allergic contact dermatitis

Bäumer

Krekeler

Devries

et al. 2006

Experimental Dermatology

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“…In vivo DX administration prior to allergen challenge has been shown to lower Langerhans numbers in lymph nodes[52]. Topical DX treatment reduced Langerhans cell size and density during afferent and efferent phases of contact sensitivity in situ [53]. Graft survival was improved with adoptive transfer of immature DC with systemic DX treatment or adoptive transfer of immature DCs treated with DX prior to transfer[54].…”

Section: Discussionmentioning

confidence: 99%

Biomaterial adjuvant effect is attenuated by anti-inflammatory drug delivery or material selection

Norton

Park

Babensee

2010

Journal of Controlled Release

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Biomaterials have been shown to differentially support dendritic cell (DC) maturation, a prerequisite for an adjuvant effect. Treatment of DCs with poly(D,L-lactic-co-glycolic acid). (PLGA) films resulted in DC maturation but agarose films did not. In these studies, the biomaterial adjuvant effect was attenuated by material selection (PLGA or agarose scaffolds) or local delivery of an anti-inflammatory/immunosuppressive glucocorticoid, dexamethasone (DX), from PLGA scaffolds. Porous scaffolds (SCs) of PLGA or agarose were produced to deliver equivalent amounts of model antigen, ovalbumin (OVA). Alternatively, PLGA SCs with incorporated OVA were produced with or without DX. These SCs were implanted individually, subcutaneously, and dorsally in C57BL/6 mice. Blood was collected from mice at specific times over a 12-week duration for measurement of antibody production against OVA. Scaffolds were explanted at 12 weeks for histological examination of foreign body response. Scaffolds of PLGA, but not of agarose, were found to elicit higher antibody production against co-delivered OVA, than negative controls. Short term delivery of DX from PLGA SCs delivering OVA temporarily delayed onset of anti-OVA antibody production. More sustained release of DX at an effective dose and with an appropriate time course is expected to extend the effect of DX on the biomaterial adjuvant effect. The immunomodulatory ability of biomaterials to affect the immune response to co-delivered antigen is demonstrated wherein this immunomodulatory ability correlates with the observed in vitro differential effects of biomaterials on DC maturation.

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“…The turnover time of LCs in vivo is approximately 4 months [55]. LC activation manifests itself as a reduction in epidermal LC density and an increase in cell size [56]. By merely subjecting human skin explants to ex vivo culture conditions, spontaneous LC depletion can be induced [57, 58].…”

Section: Discussionmentioning

confidence: 99%

Development of an ex vivo human skin model for intradermal vaccination: Tissue viability and Langerhans cell behaviour

Pearton

Coulman

et al. 2009

Vaccine

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The presence of resident Langerhans cells (LCs) in the epidermis makes the skin an attractive target for DNA vaccination. However, reliable animal models for cutaneous vaccination studies are limited. We demonstrate an ex vivo human skin model for cutaneous DNA vaccination which can potentially bridge the gap between pre-clinical in vivo animal models and clinical studies. Cutaneous transgene expression was utilised to demonstrate epidermal tissue viability in culture. LC response to the culture environment was monitored by immunohistochemistry. Full-thickness and split-thickness skin remained genetically viable in culture for at least 72 h in both phosphate-buffered saline (PBS) and full organ culture medium (OCM). The epidermis of explants cultured in OCM remained morphologically intact throughout the culture duration. LCs in full-thickness skin exhibited a delayed response (reduction in cell number and increase in cell size) to the culture conditions compared with split-thickness skin, whose response was immediate. In conclusion, excised human skin can be cultured for a minimum of 72 h for analysis of gene expression and immune cell activation. However, the use of split-thickness skin for vaccine formulation studies may not be appropriate because of the nature of the activation. Full-thickness skin explants are a more suitable model to assess cutaneous vaccination ex vivo.

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Activation Pattern of Langerhans Cells in the Afferent and Efferent Phases of Contact Hypersensitivity

Cited by 6 publications

References 53 publications

Non‐steroidal and steroidal anti‐inflammatory drugs vary in their modulation of dendritic cell function in the elicitation phase of allergic contact dermatitis

Non‐steroidal and steroidal anti‐inflammatory drugs vary in their modulation of dendritic cell function in the elicitation phase of allergic contact dermatitis

Biomaterial adjuvant effect is attenuated by anti-inflammatory drug delivery or material selection

Development of an ex vivo human skin model for intradermal vaccination: Tissue viability and Langerhans cell behaviour

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