Bifidobacterium longum의 비만세포 활성 조절능력을 통한 음식물 알레르기의 면역제어

Abstract

Allergic disease are common and represent an important source of patient morbidity. Many studies indicate that the prevalence of allergic disease such as asthma and atopic dermatitis have increased in recent decades in many western countries. Over the last decade other systemic allergic conditions including anaphylaxis and food allergy also appear to be increasing. Many groups have tried to develop the suitable treatment. In the first part, I examined whether Bifidobacterium longum KACC 91563and Enterococcus faecalis KACC 91532 have capacity to suppress food allergies. Recently, probioticshave been studied for the prevention and treatment of allergic disease. The incidence of food allergies has increased dramatically during the last decade. B. longum KACC 91563 and E. faecalis KACC 91532 were administered to BALB/c wild type mice, in which food allergy was induced using OVA and alum. Food allergy symptoms and various immune responses were assessed. B. longum KACC 91563, but not E.faecalis KACC 91532, alleviated food allergy symptoms. Extracellular vesicles (EVs) of B. longum KACC 91563 bound specifically to mast cells and induced apoptosis without affecting T cell immune responses. Further, injection of family 5 extracellular solute-binding protein (ESBP), a main component of EVs, into mice markedly reduced the occurrence of diarrhea in a mouse food allergy model. B. longum KACC 91563 induces apoptosis of mast cells specifically and alleviates food allergy symptoms. Accordingly, B. longum KACC 91563 and ESBP exhibit potential as therapeutic approaches for food allergies. In the second part, I hypothesized AD might also be attenuated in elevated levels of ROS throughtissue hyperoxygenation, such as by hyperbaric oxygen therapy (HBOT) or applying an oxygen-carryingchemical, perfluorodecalin (PFD). Because one study recently demonstrated ROS prevented imiquimod-induced psoriatic dermatitis through enhancing regulatory T cell function. Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from excessive stimulation of immune cells. Traditionally, reactive oxygen species (ROS) have been implicated in the progression of inflammatory diseases,but several opposing observations suggest the protective role of ROS in inflammatory disease. Elevated levels of ROS in the skin have been demonstrated directly by staining with dihydroethidum as well as indirectly by immunohistochemistry (IHC) for indoleamine 2,3-dioxygenase (IDO). A murine model of AD was developed by repeated application of a chemical irritant (1% 2,4-dinitrochlorobenzene) andhouse dust mite (Dermatophagoide farinae) extract on an ear of BALB/c mice. The results showed treatment with HBOT or PFD significantly attenuated AD, comparably with 0.1% prednicarbate without any signs ofside effects, such as telangiectasia. The expressions of interleukin-17A and interferon-? were alsodecreased in the AD lesions by treatment with HBOT or PFD. Enhanced expression of IDO and reduced level of hypoxia-inducible factor-1?, in association with increased frequency of FoxP3+ regulatory T cells in the AD lesions, might be involved in the underlying mechanism of oxygen therapy. Taken together, it was suggested that tissue hyperoxygenation, through HBOT or treatment with PFD, might attenuate AD through enhancing skin ROS level. Here, I suggested novel mechanism of attenuating the allergic disease by immune modulation. Despite numerous attempts at clinical approaches to cure allergicdiseases and a growing commercial market, there are few viable treatment options. Our research suggests that proteins derived from EVs might be a novel treatment option for allergic diseases targeting mast cells. I also investigated the therapeutic effects of oxygen therapy for AD, by applying HBOTor PFD after establishment of AD.