TY - JOUR
T1 - Mechanisms of inflammation in neutrophil-mediated skin diseases
AU - Marzano, Angelo V.
AU - Ortega-Loayza, Alex G.
AU - Heath, Michael
AU - Morse, Daniel
AU - Genovese, Giovanni
AU - Cugno, Massimo
N1 - Publisher Copyright:
Copyright © 2019 Marzano, Ortega-Loayza, Heath, Morse, Genovese and Cugno. 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
Y1 - 2019
N2 - Neutrophil-mediated skin diseases, originally named neutrophilic dermatoses (NDs), are a group of conditions due to an altered neutrophil recruitment and activation, characterized by polymorphic cutaneous manifestations with possible internal organ involvement. Although a number of diseases are included in this setting, the two prototypic forms are pyoderma gangrenosum (PG) and Sweet's syndrome (SS) which usually present with skin ulcers and plaque-type lesions, respectively. They have central features significantly overlapping with autoinflammatory conditions which manifest as repeated episodes of tissue inflammation. However, in contrast to appropriate inflammatory responses to insults or to autoimmune disease, there is an absence of identifiable pathogens, autoantibodies, or autoreactive lymphocytes. The recognition of monogenic autoinflammatory diseases which can present with NDs has led to study several genes involved in autoinflammation in NDs. Based on discovering of a number of mutations involving different autoinflammatory genes, neutrophil-mediated skin diseases are nowadays regarded as a spectrum of polygenic autoinflammatory conditions. Although disease mechanisms have not yet been completely elucidated, NDs are recognized as diseases involving dysfunctional cellular signaling mediated by pathways mainly related to inflammasome and IL-1 with the contributory role of IL-17 and other effector molecules. The precise elucidation of the above-mentioned pathologic mechanisms may pave the way to tailored treatments for patients with different neutrophil-mediated skin diseases.
AB - Neutrophil-mediated skin diseases, originally named neutrophilic dermatoses (NDs), are a group of conditions due to an altered neutrophil recruitment and activation, characterized by polymorphic cutaneous manifestations with possible internal organ involvement. Although a number of diseases are included in this setting, the two prototypic forms are pyoderma gangrenosum (PG) and Sweet's syndrome (SS) which usually present with skin ulcers and plaque-type lesions, respectively. They have central features significantly overlapping with autoinflammatory conditions which manifest as repeated episodes of tissue inflammation. However, in contrast to appropriate inflammatory responses to insults or to autoimmune disease, there is an absence of identifiable pathogens, autoantibodies, or autoreactive lymphocytes. The recognition of monogenic autoinflammatory diseases which can present with NDs has led to study several genes involved in autoinflammation in NDs. Based on discovering of a number of mutations involving different autoinflammatory genes, neutrophil-mediated skin diseases are nowadays regarded as a spectrum of polygenic autoinflammatory conditions. Although disease mechanisms have not yet been completely elucidated, NDs are recognized as diseases involving dysfunctional cellular signaling mediated by pathways mainly related to inflammasome and IL-1 with the contributory role of IL-17 and other effector molecules. The precise elucidation of the above-mentioned pathologic mechanisms may pave the way to tailored treatments for patients with different neutrophil-mediated skin diseases.
KW - Autoinflammation
KW - Cytokines
KW - Inflammasome
KW - Neutrophil-mediated skin diseases
KW - Pyoderma gangrenosum
UR - http://www.scopus.com/inward/record.url?scp=85067271577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067271577&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2019.01059
DO - 10.3389/fimmu.2019.01059
M3 - Review article
C2 - 31139187
AN - SCOPUS:85067271577
SN - 1664-3224
VL - 10
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - MAY
M1 - 1059
ER -