THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASIS

Over last decade, the importance of immune mechanisms for development of psoriasis has expanded considerably. This review describes biological properties of the cytokines from the interleukin-36 (IL-36) family, and their role in pathogenesis of plaque psoriasis, generalized pustular psoriasis and ps...

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Main Authors: A. Yu. Pashkin, E. I. Vorobyeva, V. R. Khairutdinov, I. E. Belousova, A. V. Samtsov, A. V. Garabagiou
Format: Article
Language:Russian
Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 2018-03-01
Series:Медицинская иммунология
Subjects:
Online Access:https://www.mimmun.ru/mimmun/article/view/1478
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author A. Yu. Pashkin
E. I. Vorobyeva
V. R. Khairutdinov
I. E. Belousova
A. V. Samtsov
A. V. Garabagiou
author_facet A. Yu. Pashkin
E. I. Vorobyeva
V. R. Khairutdinov
I. E. Belousova
A. V. Samtsov
A. V. Garabagiou
author_sort A. Yu. Pashkin
collection DOAJ
description Over last decade, the importance of immune mechanisms for development of psoriasis has expanded considerably. This review describes biological properties of the cytokines from the interleukin-36 (IL-36) family, and their role in pathogenesis of plaque psoriasis, generalized pustular psoriasis and psoriatic arthritis. Keratinocytes and dendritic cells (DC) are the main sources of IL-36 in the skin. Production of this cytokine is greatly enhanced by inflammation. The studies have shown that, in affected skin of psoriatic patients, an increased expression of IL-36α and IL-36γ is observed. IL-36γ can be considered a specific marker of psoriasis, which is not found in other inflammatory skin diseases (neurodermatitis, lichen planus, eczema). The levels of this cytokine correlate with severity of psoriasis and decreases after anti-TNFα therapy. High level of IL-36 cytokines in the areas of psoriatic eruptions correlates with increased concentrations of pro-inflammatory TNFα, IL-17, IL-22 and IFNγ in the skin. We present literature data on the role of IL-36RN mutation which encodes the IL-36ra receptor antagonist, playing a role in the development of generalized pustular psoriasis (GPP). Excessive activity of IL-36 agonists leading to accumulation of neutrophilic granulocytes in epidermis may be a key event in the GPP pathogenesis. The article deals with modern ideas about the role of neutrophilic granulocytes in development of chronic inflammatory processes underlying pathogenesis of psoriasis. Proteases of neutrophils (cathepsin G, elastase and proteinase-3) are potent IL-36 activating enzymes that increase activity of IL-36 cytokines up to 500 times. In this review, a new mechanism (netosis) is suggested for the role of neutrophils in immune response. During the netosis, a large number of cytokines, antimicrobial peptides, intracellular components, serine proteases are released into the extracellular space. Thus, they may be involved into initiation and maintenance of a chronic inflammatory process in psoriasis.The present information concerning a role of new IL-36 family cytokines as one of the main psoriasis mediators has opened new therapeutic goals for the treatment of this disease and development of new methods of targeted therapy. Specific blocking of IL-36R signaling, or inhibition of neutrophil proteases of cathepsin G, neutrophil elastase that activate members of the IL-36 family, is likely to be a successful strategy in the therapy of psoriasis.
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spelling doaj.art-c231f3ef4f894aea9f270ac0d55780562024-04-22T13:07:42ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2018-03-0120216317010.15789/1563-0625-2018-2-163-170994THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASISA. Yu. Pashkin0E. I. Vorobyeva1V. R. Khairutdinov2I. E. Belousova3A. V. Samtsov4A. V. Garabagiou5S.M. Kirov Military Medical AcademySt. Petersburg State Technological Institute (Technical University)S.M. Kirov Military Medical AcademyS.M. Kirov Military Medical AcademyS.M. Kirov Military Medical AcademySt. Petersburg State Technological Institute (Technical University)Over last decade, the importance of immune mechanisms for development of psoriasis has expanded considerably. This review describes biological properties of the cytokines from the interleukin-36 (IL-36) family, and their role in pathogenesis of plaque psoriasis, generalized pustular psoriasis and psoriatic arthritis. Keratinocytes and dendritic cells (DC) are the main sources of IL-36 in the skin. Production of this cytokine is greatly enhanced by inflammation. The studies have shown that, in affected skin of psoriatic patients, an increased expression of IL-36α and IL-36γ is observed. IL-36γ can be considered a specific marker of psoriasis, which is not found in other inflammatory skin diseases (neurodermatitis, lichen planus, eczema). The levels of this cytokine correlate with severity of psoriasis and decreases after anti-TNFα therapy. High level of IL-36 cytokines in the areas of psoriatic eruptions correlates with increased concentrations of pro-inflammatory TNFα, IL-17, IL-22 and IFNγ in the skin. We present literature data on the role of IL-36RN mutation which encodes the IL-36ra receptor antagonist, playing a role in the development of generalized pustular psoriasis (GPP). Excessive activity of IL-36 agonists leading to accumulation of neutrophilic granulocytes in epidermis may be a key event in the GPP pathogenesis. The article deals with modern ideas about the role of neutrophilic granulocytes in development of chronic inflammatory processes underlying pathogenesis of psoriasis. Proteases of neutrophils (cathepsin G, elastase and proteinase-3) are potent IL-36 activating enzymes that increase activity of IL-36 cytokines up to 500 times. In this review, a new mechanism (netosis) is suggested for the role of neutrophils in immune response. During the netosis, a large number of cytokines, antimicrobial peptides, intracellular components, serine proteases are released into the extracellular space. Thus, they may be involved into initiation and maintenance of a chronic inflammatory process in psoriasis.The present information concerning a role of new IL-36 family cytokines as one of the main psoriasis mediators has opened new therapeutic goals for the treatment of this disease and development of new methods of targeted therapy. Specific blocking of IL-36R signaling, or inhibition of neutrophil proteases of cathepsin G, neutrophil elastase that activate members of the IL-36 family, is likely to be a successful strategy in the therapy of psoriasis.https://www.mimmun.ru/mimmun/article/view/1478psoriasisimmune responseil-36 family interleukinsneutrophilic granulocytesneutrophilic extracellular trapsserine proteases
spellingShingle A. Yu. Pashkin
E. I. Vorobyeva
V. R. Khairutdinov
I. E. Belousova
A. V. Samtsov
A. V. Garabagiou
THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASIS
Медицинская иммунология
psoriasis
immune response
il-36 family interleukins
neutrophilic granulocytes
neutrophilic extracellular traps
serine proteases
title THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASIS
title_full THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASIS
title_fullStr THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASIS
title_full_unstemmed THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASIS
title_short THE ROLE OF CYTOKINES OF INTERLEUKIN 36 FAMILY IN IMMUNOPATHOGENESIS OF PSORIASIS
title_sort role of cytokines of interleukin 36 family in immunopathogenesis of psoriasis
topic psoriasis
immune response
il-36 family interleukins
neutrophilic granulocytes
neutrophilic extracellular traps
serine proteases
url https://www.mimmun.ru/mimmun/article/view/1478
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