Abstract
Bullous pemphigoid (BP) is an autoimmune and inflammatory skin disease associated with subepidermal blistering and autoantibodies directed against the hemidesmosomal components BP180 and BP230. Animal models of BP were developed by passively transferring anti-BP180 IgG into mice, which recapitulates the key features of human BP. By using these in vivo model systems, key cellular and molecular events leading to the BP disease phenotype are identified, including binding of pathogenic IgG to its target, complement activation of the classical pathway, mast cell degranulation, and infiltration and activation of neutrophils. Proteinases released by infiltrating neutrophils cleave BP180 and other hemidesmosome-associated proteins, causing DEJ separation. Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP. BP animal model evidence also implicates mast cells in the pathogenesis of BP. However, recent studies questioned the pathogenic role of mast cells in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and epidermolysis bullosa acquisita. This review highlights the current knowledge on BP pathophysiology with a focus on a potential role for mast cells in BP and mast cell-related critical issues needing to be addressed in the future.
Highlights
Specialty section: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology
We presented several lines of Bullous pemphigoid (BP) animal model evidence, together with clinical observations, implicating that MAST CELLS (MCs) are likely to be involved in the immunopathogenesis of BP
Based on the observed discrepancies in different MC-deficient models of EAE, rheumatoid arthritis (RA), and epidermolysis bullosa acquisita (EBA), it is necessary to perform anti-BP180 IgG-induced BP studies in KIT-independent MC-specific deletion strains to clarify whether MCs play a role in BP
Summary
Mast cells express KIT (CD117) and FcεRI on their surface, which are the receptors of SCF and IgE, respectively. MCs express other cell surface receptors, including IgG receptors (FcγRIII, FcγRIIa, and FcγRI), C3a and C5a receptors (C5aRs), Toll-like receptors, and receptors for many cytokines/chemokines [3]. These receptors mediate activation of MCs. Upon activation, MCs release their mediators to the homing sites, which act in host defense and various pathological conditions [4]. MCs IN NON-SKIN AUTOIMMUNE DISEASES MULTIPLE SCLEROSIS (MS) AND RHEUMATOID ARTHRITIS. Mast cells have been considered as key effector cells in many immune activities, especially IgE-associated immune responses, including host defense to parasites, allergic diseases, chronic inflammatory disorders [10, 11], and cancer [12, 13]. K/BxN mouse serum contains autoantibodies against the glucose6-phosphate isomerase and, when passively transferred to mice, induces experimental RA [30]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
