Yin-Yang of IL-33 in Human Skin Mast Cells: Reduced Degranulation, but Augmented Histamine Synthesis through p38 Activation

Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defin...

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Published in:Journal of investigative dermatology Vol. 139; no. 7; p. 1516
Main Authors: Babina, Magda, Wang, Zhao, Franke, Kristin, Guhl, Sven, Artuc, Metin, Zuberbier, Torsten
Format: Journal Article
Language:English
Published: United States 01.07.2019
Subjects:
Cell Cycle
Cell Degranulation
Cells, Cultured
Histamine - biosynthesis
Histidine Decarboxylase - metabolism
Humans
Hypersensitivity - immunology
Immunoglobulin E - metabolism
Inflammation - immunology
Interleukin-33 - metabolism
Mast Cells - metabolism
Mast Cells - pathology
p38 Mitogen-Activated Protein Kinases - genetics
p38 Mitogen-Activated Protein Kinases - metabolism
Receptors, IgE - metabolism
RNA Interference
Skin - pathology
Skin Diseases - immunology
Yin-Yang
ISSN:1523-1747, 1523-1747
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Abstract Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defined, especially upon chronic exposure to IL-33. Mimicking the inflammatory milieu of skin disorders, we found that persistent exposure to IL-33 (over a 5-week period) strengthened skin MC numbers through accelerated cell-cycle progression and restriction of apoptosis. Conversely, IL-33 attenuated degranulation and FcεRI expression, potentially as a feedback to chronic "alarmin" exposure. Interestingly, the negative impact on histamine release was counterbalanced by amplified histamine production. Considering the clinical significance of histamine and scarce information on its regulation, we explored the molecular underpinnings. IL-33 induced swift phosphorylation of p38 and JNK (but not of ERK1/2 or AKT), and stimulated histidine decarboxylase expression. Combining pharmacological inhibition and kinase elimination by Accell-facilitated RNA interference in skin MCs revealed a p38-dependent, but JNK-independent mechanism. Collectively, IL-33 exerts multifaceted effects on cutaneous MCs at a post-maturation stage. The IL-33-skin MC axis may contribute to and balance inflammation in chronic skin disorders.
AbstractList Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defined, especially upon chronic exposure to IL-33. Mimicking the inflammatory milieu of skin disorders, we found that persistent exposure to IL-33 (over a 5-week period) strengthened skin MC numbers through accelerated cell-cycle progression and restriction of apoptosis. Conversely, IL-33 attenuated degranulation and FcεRI expression, potentially as a feedback to chronic "alarmin" exposure. Interestingly, the negative impact on histamine release was counterbalanced by amplified histamine production. Considering the clinical significance of histamine and scarce information on its regulation, we explored the molecular underpinnings. IL-33 induced swift phosphorylation of p38 and JNK (but not of ERK1/2 or AKT), and stimulated histidine decarboxylase expression. Combining pharmacological inhibition and kinase elimination by Accell-facilitated RNA interference in skin MCs revealed a p38-dependent, but JNK-independent mechanism. Collectively, IL-33 exerts multifaceted effects on cutaneous MCs at a post-maturation stage. The IL-33-skin MC axis may contribute to and balance inflammation in chronic skin disorders.
Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defined, especially upon chronic exposure to IL-33. Mimicking the inflammatory milieu of skin disorders, we found that persistent exposure to IL-33 (over a 5-week period) strengthened skin MC numbers through accelerated cell-cycle progression and restriction of apoptosis. Conversely, IL-33 attenuated degranulation and FcεRI expression, potentially as a feedback to chronic "alarmin" exposure. Interestingly, the negative impact on histamine release was counterbalanced by amplified histamine production. Considering the clinical significance of histamine and scarce information on its regulation, we explored the molecular underpinnings. IL-33 induced swift phosphorylation of p38 and JNK (but not of ERK1/2 or AKT), and stimulated histidine decarboxylase expression. Combining pharmacological inhibition and kinase elimination by Accell-facilitated RNA interference in skin MCs revealed a p38-dependent, but JNK-independent mechanism. Collectively, IL-33 exerts multifaceted effects on cutaneous MCs at a post-maturation stage. The IL-33-skin MC axis may contribute to and balance inflammation in chronic skin disorders.Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen contact. Owing to their pronounced receptor expression, MCs are important targets of IL-33 action, but consequences for skin MCs are ill-defined, especially upon chronic exposure to IL-33. Mimicking the inflammatory milieu of skin disorders, we found that persistent exposure to IL-33 (over a 5-week period) strengthened skin MC numbers through accelerated cell-cycle progression and restriction of apoptosis. Conversely, IL-33 attenuated degranulation and FcεRI expression, potentially as a feedback to chronic "alarmin" exposure. Interestingly, the negative impact on histamine release was counterbalanced by amplified histamine production. Considering the clinical significance of histamine and scarce information on its regulation, we explored the molecular underpinnings. IL-33 induced swift phosphorylation of p38 and JNK (but not of ERK1/2 or AKT), and stimulated histidine decarboxylase expression. Combining pharmacological inhibition and kinase elimination by Accell-facilitated RNA interference in skin MCs revealed a p38-dependent, but JNK-independent mechanism. Collectively, IL-33 exerts multifaceted effects on cutaneous MCs at a post-maturation stage. The IL-33-skin MC axis may contribute to and balance inflammation in chronic skin disorders.
Author Guhl, Sven
Artuc, Metin
Wang, Zhao
Zuberbier, Torsten
Franke, Kristin
Babina, Magda
Author_xml – sequence: 1
  givenname: Magda
  surname: Babina
  fullname: Babina, Magda
  email: magda.babina@charite.de
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address: magda.babina@charite.de
– sequence: 2
  givenname: Zhao
  surname: Wang
  fullname: Wang, Zhao
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
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  givenname: Kristin
  surname: Franke
  fullname: Franke, Kristin
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
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  givenname: Sven
  surname: Guhl
  fullname: Guhl, Sven
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
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  givenname: Metin
  surname: Artuc
  fullname: Artuc, Metin
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  givenname: Torsten
  surname: Zuberbier
  fullname: Zuberbier, Torsten
  organization: Department of Dermatology, Venereology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany
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Snippet Mast cells (MCs) are the principal effector cells of IgE-mediated allergy. IL-33 is released by resident skin cells as alarmin upon tissue damage or allergen...
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SubjectTerms Cell Cycle
Cell Degranulation
Cells, Cultured
Histamine - biosynthesis
Histidine Decarboxylase - metabolism
Humans
Hypersensitivity - immunology
Immunoglobulin E - metabolism
Inflammation - immunology
Interleukin-33 - metabolism
Mast Cells - metabolism
Mast Cells - pathology
p38 Mitogen-Activated Protein Kinases - genetics
p38 Mitogen-Activated Protein Kinases - metabolism
Receptors, IgE - metabolism
RNA Interference
Skin - pathology
Skin Diseases - immunology
Yin-Yang
Title Yin-Yang of IL-33 in Human Skin Mast Cells: Reduced Degranulation, but Augmented Histamine Synthesis through p38 Activation
URI https://www.ncbi.nlm.nih.gov/pubmed/30684550
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