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Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome
Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by atopic manifestations and susceptibility to infections with extracellular pathogens, typically Staphylococcus aureus, which preferentially affect the skin and lung. Previous studies reported the defective differentiation of T h...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715068/ https://www.ncbi.nlm.nih.gov/pubmed/19487419 http://dx.doi.org/10.1084/jem.20082767 |
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author | Minegishi, Yoshiyuki Saito, Masako Nagasawa, Masayuki Takada, Hidetoshi Hara, Toshiro Tsuchiya, Shigeru Agematsu, Kazunaga Yamada, Masafumi Kawamura, Nobuaki Ariga, Tadashi Tsuge, Ikuya Karasuyama, Hajime |
author_facet | Minegishi, Yoshiyuki Saito, Masako Nagasawa, Masayuki Takada, Hidetoshi Hara, Toshiro Tsuchiya, Shigeru Agematsu, Kazunaga Yamada, Masafumi Kawamura, Nobuaki Ariga, Tadashi Tsuge, Ikuya Karasuyama, Hajime |
author_sort | Minegishi, Yoshiyuki |
collection | PubMed |
description | Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by atopic manifestations and susceptibility to infections with extracellular pathogens, typically Staphylococcus aureus, which preferentially affect the skin and lung. Previous studies reported the defective differentiation of T helper 17 (Th17) cells in HIES patients caused by hypomorphic STAT3 mutations. However, the apparent contradiction between the systemic Th17 deficiency and the skin/lung-restricted susceptibility to staphylococcal infections remains puzzling. We present a possible molecular explanation for this enigmatic contradiction. HIES T cells showed impaired production of Th17 cytokines but normal production of classical proinflammatory cytokines including interleukin 1β. Normal human keratinocytes and bronchial epithelial cells were deeply dependent on the synergistic action of Th17 cytokines and classical proinflammatory cytokines for their production of antistaphylococcal factors, including neutrophil-recruiting chemokines and antimicrobial peptides. In contrast, other cell types were efficiently stimulated with the classical proinflammatory cytokines alone to produce such factors. Accordingly, keratinocytes and bronchial epithelial cells, unlike other cell types, failed to produce antistaphylococcal factors in response to HIES T cell–derived cytokines. These results appear to explain, at least in part, why HIES patients suffer from recurrent staphylococcal infections confined to the skin and lung in contrast to more systemic infections in neutrophil-deficient patients. |
format | Text |
id | pubmed-2715068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27150682009-12-08 Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome Minegishi, Yoshiyuki Saito, Masako Nagasawa, Masayuki Takada, Hidetoshi Hara, Toshiro Tsuchiya, Shigeru Agematsu, Kazunaga Yamada, Masafumi Kawamura, Nobuaki Ariga, Tadashi Tsuge, Ikuya Karasuyama, Hajime J Exp Med Article Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by atopic manifestations and susceptibility to infections with extracellular pathogens, typically Staphylococcus aureus, which preferentially affect the skin and lung. Previous studies reported the defective differentiation of T helper 17 (Th17) cells in HIES patients caused by hypomorphic STAT3 mutations. However, the apparent contradiction between the systemic Th17 deficiency and the skin/lung-restricted susceptibility to staphylococcal infections remains puzzling. We present a possible molecular explanation for this enigmatic contradiction. HIES T cells showed impaired production of Th17 cytokines but normal production of classical proinflammatory cytokines including interleukin 1β. Normal human keratinocytes and bronchial epithelial cells were deeply dependent on the synergistic action of Th17 cytokines and classical proinflammatory cytokines for their production of antistaphylococcal factors, including neutrophil-recruiting chemokines and antimicrobial peptides. In contrast, other cell types were efficiently stimulated with the classical proinflammatory cytokines alone to produce such factors. Accordingly, keratinocytes and bronchial epithelial cells, unlike other cell types, failed to produce antistaphylococcal factors in response to HIES T cell–derived cytokines. These results appear to explain, at least in part, why HIES patients suffer from recurrent staphylococcal infections confined to the skin and lung in contrast to more systemic infections in neutrophil-deficient patients. The Rockefeller University Press 2009-06-08 /pmc/articles/PMC2715068/ /pubmed/19487419 http://dx.doi.org/10.1084/jem.20082767 Text en © 2009 Minegishi 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 Minegishi, Yoshiyuki Saito, Masako Nagasawa, Masayuki Takada, Hidetoshi Hara, Toshiro Tsuchiya, Shigeru Agematsu, Kazunaga Yamada, Masafumi Kawamura, Nobuaki Ariga, Tadashi Tsuge, Ikuya Karasuyama, Hajime Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome |
title | Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome |
title_full | Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome |
title_fullStr | Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome |
title_full_unstemmed | Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome |
title_short | Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome |
title_sort | molecular explanation for the contradiction between systemic th17 defect and localized bacterial infection in hyper-ige syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715068/ https://www.ncbi.nlm.nih.gov/pubmed/19487419 http://dx.doi.org/10.1084/jem.20082767 |
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