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IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis

Osteoarthritis is characterized by articular cartilage breakdown, and emerging evidence suggests that dysregulated innate immunity is likely involved. Here, we performed proteomic, transcriptomic, and electron microscopic analyses to demonstrate that mast cells are aberrantly activated in human and...

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Autores principales: Wang, Qian, Lepus, Christin M, Raghu, Harini, Reber, Laurent L, Tsai, Mindy M, Wong, Heidi H, von Kaeppler, Ericka, Lingampalli, Nithya, Bloom, Michelle S, Hu, Nick, Elliott, Eileen E, Oliviero, Francesca, Punzi, Leonardo, Giori, Nicholas J, Goodman, Stuart B, Chu, Constance R, Sokolove, Jeremy, Fukuoka, Yoshihiro, Schwartz, Lawrence B, Galli, Stephen J, Robinson, William H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516833/
https://www.ncbi.nlm.nih.gov/pubmed/31084709
http://dx.doi.org/10.7554/eLife.39905
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author Wang, Qian
Lepus, Christin M
Raghu, Harini
Reber, Laurent L
Tsai, Mindy M
Wong, Heidi H
von Kaeppler, Ericka
Lingampalli, Nithya
Bloom, Michelle S
Hu, Nick
Elliott, Eileen E
Oliviero, Francesca
Punzi, Leonardo
Giori, Nicholas J
Goodman, Stuart B
Chu, Constance R
Sokolove, Jeremy
Fukuoka, Yoshihiro
Schwartz, Lawrence B
Galli, Stephen J
Robinson, William H
author_facet Wang, Qian
Lepus, Christin M
Raghu, Harini
Reber, Laurent L
Tsai, Mindy M
Wong, Heidi H
von Kaeppler, Ericka
Lingampalli, Nithya
Bloom, Michelle S
Hu, Nick
Elliott, Eileen E
Oliviero, Francesca
Punzi, Leonardo
Giori, Nicholas J
Goodman, Stuart B
Chu, Constance R
Sokolove, Jeremy
Fukuoka, Yoshihiro
Schwartz, Lawrence B
Galli, Stephen J
Robinson, William H
author_sort Wang, Qian
collection PubMed
description Osteoarthritis is characterized by articular cartilage breakdown, and emerging evidence suggests that dysregulated innate immunity is likely involved. Here, we performed proteomic, transcriptomic, and electron microscopic analyses to demonstrate that mast cells are aberrantly activated in human and murine osteoarthritic joint tissues. Using genetic models of mast cell deficiency, we demonstrate that lack of mast cells attenuates osteoarthritis in mice. Using genetic and pharmacologic approaches, we show that the IgE/FcεRI/Syk signaling axis is critical for the development of osteoarthritis. We find that mast cell-derived tryptase induces inflammation, chondrocyte apoptosis, and cartilage breakdown. Our findings demonstrate a central role for IgE-dependent mast cell activation in the pathogenesis of osteoarthritis, suggesting that targeting mast cells could provide therapeutic benefit in human osteoarthritis. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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spelling pubmed-65168332019-05-16 IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis Wang, Qian Lepus, Christin M Raghu, Harini Reber, Laurent L Tsai, Mindy M Wong, Heidi H von Kaeppler, Ericka Lingampalli, Nithya Bloom, Michelle S Hu, Nick Elliott, Eileen E Oliviero, Francesca Punzi, Leonardo Giori, Nicholas J Goodman, Stuart B Chu, Constance R Sokolove, Jeremy Fukuoka, Yoshihiro Schwartz, Lawrence B Galli, Stephen J Robinson, William H eLife Immunology and Inflammation Osteoarthritis is characterized by articular cartilage breakdown, and emerging evidence suggests that dysregulated innate immunity is likely involved. Here, we performed proteomic, transcriptomic, and electron microscopic analyses to demonstrate that mast cells are aberrantly activated in human and murine osteoarthritic joint tissues. Using genetic models of mast cell deficiency, we demonstrate that lack of mast cells attenuates osteoarthritis in mice. Using genetic and pharmacologic approaches, we show that the IgE/FcεRI/Syk signaling axis is critical for the development of osteoarthritis. We find that mast cell-derived tryptase induces inflammation, chondrocyte apoptosis, and cartilage breakdown. Our findings demonstrate a central role for IgE-dependent mast cell activation in the pathogenesis of osteoarthritis, suggesting that targeting mast cells could provide therapeutic benefit in human osteoarthritis. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter). eLife Sciences Publications, Ltd 2019-05-14 /pmc/articles/PMC6516833/ /pubmed/31084709 http://dx.doi.org/10.7554/eLife.39905 Text en © 2019, Wang et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Wang, Qian
Lepus, Christin M
Raghu, Harini
Reber, Laurent L
Tsai, Mindy M
Wong, Heidi H
von Kaeppler, Ericka
Lingampalli, Nithya
Bloom, Michelle S
Hu, Nick
Elliott, Eileen E
Oliviero, Francesca
Punzi, Leonardo
Giori, Nicholas J
Goodman, Stuart B
Chu, Constance R
Sokolove, Jeremy
Fukuoka, Yoshihiro
Schwartz, Lawrence B
Galli, Stephen J
Robinson, William H
IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis
title IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis
title_full IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis
title_fullStr IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis
title_full_unstemmed IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis
title_short IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis
title_sort ige-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516833/
https://www.ncbi.nlm.nih.gov/pubmed/31084709
http://dx.doi.org/10.7554/eLife.39905
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