The idea of a role of MC in BP was further strengthened when Delaporte et al. to clarify discrepant findings and finally elucidate the role of MCs in AIBD by summarizing and discussing the findings in both clinical and experimental studies. upregulated gene expression in response to stimulation, including most cytokines and chemokines (5). Their wide tissue distribution and broad activating capacity designates MCs as major immune cells at the body interface regulating both innate and adaptive immunity (7, 8). These properties give rise to the question whether MCs have the ability to regulate immune responses against autoantigens and in skin autoimmune diseases like AIBD. This idea has been substantiated by clinical observations in which MC activation has been shown in some AIBD, and experimentally by employing MC-deficient mice in animal models of AIBD. In this mini-review article, we summarize and discuss clinical and experimental findings to clarify the role of MCs in these diseases. MCs in Human AIBD The first evidence indicating a role of MCs in AIBD can be traced back to 1978, when Wintroub et al. investigated bullous pemphigoid (BP) (9), the most common autoimmune blistering disease characterized by autoantibodies against the autoantigens BP180 (also named type XVII collagen, COL17) and BP230 (10). Besides autoantibodies and complement deposition at MK-7246 the basement-membrane zone, they observed a progressive MC degranulation and subsequent eosinophil infiltration in affected skin of BP patients (9). This MC degranulation was associated with elevated levels of MC-derived mediators and proteases, including eosinophil chemotactic factor, in bullous fluid suggesting for the first time a role of MCs in the Rabbit Polyclonal to Claudin 5 (phospho-Tyr217) pathogenesis of BP (9). Later, Dvorak et al. confirmed this hypothesis by investigating histological changes of clinical lesions in a BP patient during pathogenesis (11). They found that the clinical lesions were featured by a sequence of histopathologic events starting with MC degranulation and proceeding to infiltration of lymphocytes and later on eosinophils and basophils. The notion of a role of MC in BP was further strengthened when Delaporte et al. discovered that most patients express IgE autoantibodies which specifically activate MCs and eosinophils (12). In 2007, Fairley transferred total IgE isolated from BP patients or healthy controls into immune-deficient mice engrafted with human skin. Twenty-four hours after IgE injection, mice receiving BP IgE, but not control IgE, showed erythematous elevated plaques, MC activation, and dermal infiltrates of inflammatory cells. Furthermore, dermal-epidermal separation, a key clinical feature of BP, was also observed in recipient mice when a high dose of patient-derived IgE was transferred (13). This evidence from humanized mice demonstrates that IgE autoantibodies in BP patients are able to promote disease manifestation, further supporting a potential role of MCs in the pathogenesis of BP. Besides BP, an involvement of MCs was also suggested in a range of other AIBD. For example, increased numbers of MCs have been detected in the skin of pemphigus vulgaris (PV) patients (14), in the conjunctiva of patients with ocular cicatricial pemphigoid (a subtype of MMP) (15), and in the lesional bullous skin of patients with linear IgA disease (LAD) (16). Moreover, activation of MCs has also been observed in some AIBD, including LAD (16), epidermolysis bullosa acquisita (EBA) (17), and PV (18). In addition, the presence of high concentrations of Dgs3-reactive IgE and intercellular IgE deposits in PV patients in the acute onset of the disease also indicates MK-7246 an involvement of MCs in PV (19). MCs in Mouse Models of AIBD Experimental Models of Autoimmune Blistering Diseases Animal models have been established for different AIBD, such as BP, EBA, and PV diverse strategies namely immunization with autoantigen, transfer of autoantibodies or autoreactive lymphocytes, and genetic modification (20). These animal models have been extensively used for investigation of disease pathogenesis (20), including the role of MCs. Here, we highlight those animal models which have been used for studying the role of MCs in AIBD MK-7246 (17, 21). In 1993, Liu and his colleagues for the first time established.