TY - JOUR
T1 - Proteases in pemphigoid diseases
AU - Hiroyasu, Sho
AU - Turner, Christopher T.
AU - Richardson, Katlyn C.
AU - Granville, David J.
N1 - Funding Information:
We appreciate Drs. Daisuke Tsuruta and Takashi Hashimoto for their valuable comments. This work was supported by grants-in-aid from the Canadian Institutes for Health Research (CIHR) (DG) and Michael Smith Foundation for Health Research (DG). CT is funded by a CIHR post-doctoral fellowship (F16-05378).
Publisher Copyright:
Copyright © 2019 Hiroyasu, Turner, Richardson and Granville. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
PY - 2019/6/26
Y1 - 2019/6/26
N2 - Pemphigoid diseases are a subgroup of autoimmune skin diseases characterized by widespread tense blisters. Standard of care typically involves immunosuppressive treatments, which may be insufficient and are often associated with significant adverse events. As such, a deeper understanding of the pathomechanism(s) of pemphigoid diseases is necessary in order to identify improved therapeutic approaches. A major initiator of pemphigoid diseases is the accumulation of autoantibodies against proteins at the dermal-epidermal junction (DEJ), followed by protease activation at the lesion. The contribution of proteases to pemphigoid disease pathogenesis has been investigated using a combination of in vitro and in vivo models. These studies suggest proteolytic degradation of anchoring proteins proximal to the DEJ is crucial for dermal-epidermal separation and blister formation. In addition, proteases can also augment inflammation, expose autoantigenic cryptic epitopes, and/or provoke autoantigen spreading, which are all important in pemphigoid disease pathology. The present review summarizes and critically evaluates the current understanding with respect to the role of proteases in pemphigoid diseases.
AB - Pemphigoid diseases are a subgroup of autoimmune skin diseases characterized by widespread tense blisters. Standard of care typically involves immunosuppressive treatments, which may be insufficient and are often associated with significant adverse events. As such, a deeper understanding of the pathomechanism(s) of pemphigoid diseases is necessary in order to identify improved therapeutic approaches. A major initiator of pemphigoid diseases is the accumulation of autoantibodies against proteins at the dermal-epidermal junction (DEJ), followed by protease activation at the lesion. The contribution of proteases to pemphigoid disease pathogenesis has been investigated using a combination of in vitro and in vivo models. These studies suggest proteolytic degradation of anchoring proteins proximal to the DEJ is crucial for dermal-epidermal separation and blister formation. In addition, proteases can also augment inflammation, expose autoantigenic cryptic epitopes, and/or provoke autoantigen spreading, which are all important in pemphigoid disease pathology. The present review summarizes and critically evaluates the current understanding with respect to the role of proteases in pemphigoid diseases.
KW - Bullous pemphigoid
KW - Elastase
KW - Epidermolysis bullosa acquisita
KW - Granzyme
KW - MMP
KW - Mucous membrane pemphigoid
KW - Pemphigoid diseases
KW - Proteases
UR - http://www.scopus.com/inward/record.url?scp=85069038748&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2019.01454
DO - 10.3389/fimmu.2019.01454
M3 - Review Article
C2 - 31297118
AN - SCOPUS:85069038748
SN - 1664-3224
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - JUN
M1 - 1454
ER -