Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions |
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Authors: | Jeong Young-Il Kim Seung Hyun Ju Jung Won Cho Shin Hyeong Lee Won Ja Park Jin Wook Park Yeong-Min Lee Sang Eun |
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Institution: | aDiv. of Malaria & Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong, Republic of Korea;bDiv. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong, Republic of Korea;cDept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San, Republic of Korea |
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Abstract: | Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4+CD25+Foxp3+ regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naïve T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and helminth infection. |
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Keywords: | Clonorchis sinensis Asthma Hygiene hypothesis Regulatory T cell Dendritic cell |
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