Generalized Pustular Psoriasis: Divergence of Innate and Adaptive Immunity
Generalized pustular psoriasis (GPP) is a severe, relapsing, immune-mediated disease characterized by the presence of multiple sterile pustules all over the body. The exact pathomechanisms behind GPP remain elusive, although increased interest in the genetic basis and immunological disturbances have...
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doaj-28205a21c23649e397d2384af93071b52021-08-26T13:53:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-01229048904810.3390/ijms22169048Generalized Pustular Psoriasis: Divergence of Innate and Adaptive ImmunityDominik Samotij0Justyna Szczęch1Adam Reich2Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University ul. Fryderyka Szopena 2, 35-055 Rzeszów, PolandDepartment of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University ul. Fryderyka Szopena 2, 35-055 Rzeszów, PolandDepartment of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University ul. Fryderyka Szopena 2, 35-055 Rzeszów, PolandGeneralized pustular psoriasis (GPP) is a severe, relapsing, immune-mediated disease characterized by the presence of multiple sterile pustules all over the body. The exact pathomechanisms behind GPP remain elusive, although increased interest in the genetic basis and immunological disturbances have provided some revealing insights into the underlying signaling pathways and their mutual interaction. The genetic background of GPP has been thoroughly investigated over the past few years. The conducted studies have identified genetic variants that predispose to pustular forms of psoriasis. The loss-of-function mutation of the interleukin 36 receptor antagonist gene, along with rare gain-of-function mutations in the gene that encodes the keratinocyte signaling molecule (CARD14), are examples of the uncovered abnormalities. Interleukin 36 (IL-36), along with neutrophils, is now considered a central cytokine in GPP pathogenesis, with IL-36 signaling providing a link between innate and adaptive immune responses. More recently, a new concept of inflammation, caused by a predominantly genetically determined abnormal activation of innate immune response and leading to inflammatory keratinization, has arisen. GPP is currently considered a representative of this novel group of skin conditions, called autoinflammatory keratinization diseases. As no therapeutic agents have been approved for GPP to date in the United States and Europe, the novel anti-IL-36R antibodies are particularly promising and may revolutionize management of the disease.https://www.mdpi.com/1422-0067/22/16/9048generalized pustular psoriasisvon ZumbuschIL-36autoinflammationinnate immunitygenetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dominik Samotij Justyna Szczęch Adam Reich |
spellingShingle |
Dominik Samotij Justyna Szczęch Adam Reich Generalized Pustular Psoriasis: Divergence of Innate and Adaptive Immunity International Journal of Molecular Sciences generalized pustular psoriasis von Zumbusch IL-36 autoinflammation innate immunity genetics |
author_facet |
Dominik Samotij Justyna Szczęch Adam Reich |
author_sort |
Dominik Samotij |
title |
Generalized Pustular Psoriasis: Divergence of Innate and Adaptive Immunity |
title_short |
Generalized Pustular Psoriasis: Divergence of Innate and Adaptive Immunity |
title_full |
Generalized Pustular Psoriasis: Divergence of Innate and Adaptive Immunity |
title_fullStr |
Generalized Pustular Psoriasis: Divergence of Innate and Adaptive Immunity |
title_full_unstemmed |
Generalized Pustular Psoriasis: Divergence of Innate and Adaptive Immunity |
title_sort |
generalized pustular psoriasis: divergence of innate and adaptive immunity |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-08-01 |
description |
Generalized pustular psoriasis (GPP) is a severe, relapsing, immune-mediated disease characterized by the presence of multiple sterile pustules all over the body. The exact pathomechanisms behind GPP remain elusive, although increased interest in the genetic basis and immunological disturbances have provided some revealing insights into the underlying signaling pathways and their mutual interaction. The genetic background of GPP has been thoroughly investigated over the past few years. The conducted studies have identified genetic variants that predispose to pustular forms of psoriasis. The loss-of-function mutation of the interleukin 36 receptor antagonist gene, along with rare gain-of-function mutations in the gene that encodes the keratinocyte signaling molecule (CARD14), are examples of the uncovered abnormalities. Interleukin 36 (IL-36), along with neutrophils, is now considered a central cytokine in GPP pathogenesis, with IL-36 signaling providing a link between innate and adaptive immune responses. More recently, a new concept of inflammation, caused by a predominantly genetically determined abnormal activation of innate immune response and leading to inflammatory keratinization, has arisen. GPP is currently considered a representative of this novel group of skin conditions, called autoinflammatory keratinization diseases. As no therapeutic agents have been approved for GPP to date in the United States and Europe, the novel anti-IL-36R antibodies are particularly promising and may revolutionize management of the disease. |
topic |
generalized pustular psoriasis von Zumbusch IL-36 autoinflammation innate immunity genetics |
url |
https://www.mdpi.com/1422-0067/22/16/9048 |
work_keys_str_mv |
AT dominiksamotij generalizedpustularpsoriasisdivergenceofinnateandadaptiveimmunity AT justynaszczech generalizedpustularpsoriasisdivergenceofinnateandadaptiveimmunity AT adamreich generalizedpustularpsoriasisdivergenceofinnateandadaptiveimmunity |
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