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Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria

Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti–interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β...

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Autores principales: Nakamura, Yuumi, Kambe, Naotomo, Saito, Megumu, Nishikomori, Ryuta, Kim, Yun-Gi, Murakami, Makoto, Núñez, Gabriel, Matsue, Hiroyuki
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715029/
https://www.ncbi.nlm.nih.gov/pubmed/19364881
http://dx.doi.org/10.1084/jem.20082179
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author Nakamura, Yuumi
Kambe, Naotomo
Saito, Megumu
Nishikomori, Ryuta
Kim, Yun-Gi
Murakami, Makoto
Núñez, Gabriel
Matsue, Hiroyuki
author_facet Nakamura, Yuumi
Kambe, Naotomo
Saito, Megumu
Nishikomori, Ryuta
Kim, Yun-Gi
Murakami, Makoto
Núñez, Gabriel
Matsue, Hiroyuki
author_sort Nakamura, Yuumi
collection PubMed
description Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti–interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β in the skin. However, the cellular mechanisms regulating IL-1β production in the skin of CAPS patients remain unclear. We identified mast cells (MCs) as the main cell population responsible for IL-1β production in the skin of CAPS patients. Unlike normal MCs that required stimulation with proinflammatory stimuli for IL-1β production, resident MCs from CAPS patients constitutively produced IL-1β. Primary MCs expressed inflammasome components and secreted IL-1β via NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain when stimulated with microbial stimuli known to activate caspase-1. Furthermore, MCs expressing disease-associated but not wild-type NLRP3 secreted IL-1β and induced neutrophil migration and vascular leakage, the histological hallmarks of urticarial rash, when transplanted into mouse skin. Our findings implicate MCs as IL-1β producers in the skin and mediators of histamine-independent urticaria through the NLRP3 inflammasome.
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spelling pubmed-27150292009-11-11 Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria Nakamura, Yuumi Kambe, Naotomo Saito, Megumu Nishikomori, Ryuta Kim, Yun-Gi Murakami, Makoto Núñez, Gabriel Matsue, Hiroyuki J Exp Med Article Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti–interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β in the skin. However, the cellular mechanisms regulating IL-1β production in the skin of CAPS patients remain unclear. We identified mast cells (MCs) as the main cell population responsible for IL-1β production in the skin of CAPS patients. Unlike normal MCs that required stimulation with proinflammatory stimuli for IL-1β production, resident MCs from CAPS patients constitutively produced IL-1β. Primary MCs expressed inflammasome components and secreted IL-1β via NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain when stimulated with microbial stimuli known to activate caspase-1. Furthermore, MCs expressing disease-associated but not wild-type NLRP3 secreted IL-1β and induced neutrophil migration and vascular leakage, the histological hallmarks of urticarial rash, when transplanted into mouse skin. Our findings implicate MCs as IL-1β producers in the skin and mediators of histamine-independent urticaria through the NLRP3 inflammasome. The Rockefeller University Press 2009-05-11 /pmc/articles/PMC2715029/ /pubmed/19364881 http://dx.doi.org/10.1084/jem.20082179 Text en © 2009 Nakamura et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Nakamura, Yuumi
Kambe, Naotomo
Saito, Megumu
Nishikomori, Ryuta
Kim, Yun-Gi
Murakami, Makoto
Núñez, Gabriel
Matsue, Hiroyuki
Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
title Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
title_full Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
title_fullStr Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
title_full_unstemmed Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
title_short Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
title_sort mast cells mediate neutrophil recruitment and vascular leakage through the nlrp3 inflammasome in histamine-independent urticaria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715029/
https://www.ncbi.nlm.nih.gov/pubmed/19364881
http://dx.doi.org/10.1084/jem.20082179
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