Concurrent exposure to a dectin-1 agonist suppresses the Th2 response to epicutaneously introduced antigen in mice

Journal of Biomedical Science, Jan 2013

Background Epicutaneous sensitization with protein allergen that induces predominant Th2 responses is an important sensitization route in atopic dermatitis. Fungal components have been shown to modulate Th cell differentiation. However, the effects of fungal components on epicutaneous sensitization are unclear. Results In this study, we showed that co-administration of curdlan, a dectin-1 agonist, during epicutaneous ovalbumin sensitization of BALB/c mice decreased the IL-5 and IL-13 levels in supernatants of lymph node cell ovalbumin reactivation cultures. Mechanistically, curdlan co-administration decreased IL-4 and IL-1β expressions in draining lymph nodes. Curdlan co-administration also lower the migration of langerin+ CD103- epidermal Langerhans cells into draining lymph nodes at 96 hours post-sensitization which might be attributed to decreased expressions of IL-18 and IL-1β in patched skin. Moreover, adoptive transfer of CFSE-labeled transgenic CD4 T cells confirmed that curdlan co-administration decreased the proliferation and IL-4-production of ovalbumin -specific T cells primed by epidermal Langerhans cells. Conclusions These results indicated that concurrent exposure to a dectin-1 agonist suppresses the epicutaneously induced Th2 response by modulating the cytokine expression profiles in draining LNs and the migration of epidermal Langerhans cells. These results highlight the effects of fungal components on epicutaneous allergen sensitization in atopic diseases.

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Concurrent exposure to a dectin-1 agonist suppresses the Th2 response to epicutaneously introduced antigen in mice

Jing-Yi Lin 2 Jau-Shiuh Chen 0 Pei-Chun Chen 1 Ming-Hui Chung 0 Ching-Yi Liu 0 Shi-Chuen Miaw 3 Li-Fang Wang 0 0 Department of Dermatology, National Taiwan University Hospital , No.7, Chung-Shan South Road, Taipei , Taiwan 1 Department of Statistics and Informatics Science, Providence University , Taichung , Taiwan 2 Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Taoyuan , Taiwan 3 Graduate Institute of Immunology of National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei , Taiwan Background: Epicutaneous sensitization with protein allergen that induces predominant Th2 responses is an important sensitization route in atopic dermatitis. Fungal components have been shown to modulate Th cell differentiation. However, the effects of fungal components on epicutaneous sensitization are unclear. Results: In this study, we showed that co-administration of curdlan, a dectin-1 agonist, during epicutaneous ovalbumin sensitization of BALB/c mice decreased the IL-5 and IL-13 levels in supernatants of lymph node cell ovalbumin reactivation cultures. Mechanistically, curdlan co-administration decreased IL-4 and IL-1 expressions in draining lymph nodes. Curdlan co-administration also lower the migration of langerin+ CD103- epidermal Langerhans cells into draining lymph nodes at 96 hours post-sensitization which might be attributed to decreased expressions of IL-18 and IL-1 in patched skin. Moreover, adoptive transfer of CFSE-labeled transgenic CD4 T cells confirmed that curdlan co-administration decreased the proliferation and IL-4-production of ovalbumin -specific T cells primed by epidermal Langerhans cells. Conclusions: These results indicated that concurrent exposure to a dectin-1 agonist suppresses the epicutaneously induced Th2 response by modulating the cytokine expression profiles in draining LNs and the migration of epidermal Langerhans cells. These results highlight the effects of fungal components on epicutaneous allergen sensitization in atopic diseases. - Background The prevalence of atopic diseases has progressively increased in recent decades. The interaction between genetic susceptibility for atopy with varying environmental allergen exposures plays a central role in the pathogenesis of atopic diseases [1]. Allergens that provoke atopic diseases are ubiquitously distributed environmental protein antigens. Atopic dermatitis (AD) is often the first manifestation of the atopic triad and typically marks the onset of the atopic march [2]. The route of protein allergen sensitization in AD remains unclear. However, compelling clinical evidence suggests that epicutaneous exposure to protein antigen is one of the important sensitization routes for AD [3,4]. In animal models, we and others have demonstrated that epicutaneous sensitization with protein antigens induces predominate Th2 and weak Th1 responses, which leads to AD-like skin lesions and the development of asthma [5,6]. Epicutaneous sensitization with protein antigen also induces a modest Th17 response [7,8]. However, cross-priming with an epicutaneously introduced protein antigen generates Th1, but not Th2 cells [9]. An epicutaneously induced Th2 response requires the production of IL-10 and IL-13 [10,11]. Because defective IFN- production during infancy may be an important cause for sustained elevation of Th2 responses in atopic children, determining how to suppress Th2 and/or promote Th1 responses during the early sensitization period was expected to be a useful strategy to modulate the natural course of atopic diseases [12]. Severe systemic fungal infections have become an increasing problem during recent decades. The cell walls of fungi are composed, primarily, of carbohydrates, including mannoprotein, -glucan, and chitin, which can be recognized by several classes of pattern recognition receptors [13]. Among these, dectin-1, a C-type lectin receptor involved in the recognition of -glucan was shown to be crucial for the control of fungal infection [14,15]. Dectin-1 signaling in macrophages and neutrophils can trigger phagocytosis, a respiratory burst, and the production of inflammatory cytokines and chemokines, which further activate macrophages and neutrophils, thus resulting in the elimination of microorganisms [16]. Moreover, these pattern recognition receptors can drive the development of adaptive immunity. For example, signaling through dectin-1 induces dendritic cell (DC) maturation with the concomitant upregulation of co-stimulatory molecules and the secretion of IL-2, IL-10, IL-6, and TNF-, in addition to a bias for IL-23 production rather than IL-12 [17]. Dectin-1-activated DCs can instruct the differentiation of Th1 and Th17, but not Th2 cells [17,18]. Stimulation of DCs via the dectin-1 pathway also allows priming of cytotoxic T-cell responses [19]. Many fungi, such as Candida albicans, are both commensals and pathogens at the skin surface and (...truncated)


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Jing-Yi Lin, Jau-Shiuh Chen, Pei-Chun Chen, Ming-Hui Chung, Ching-Yi Liu, Shi-Chuen Miaw, Li-Fang Wang. Concurrent exposure to a dectin-1 agonist suppresses the Th2 response to epicutaneously introduced antigen in mice, Journal of Biomedical Science, 2013, pp. 1, 20, DOI: 10.1186/1423-0127-20-1