Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction

被引:62
作者
Bosco, A. [1 ,2 ]
Ehteshami, S. [1 ,2 ]
Stern, D. A. [1 ,2 ]
Martinez, F. D. [1 ,2 ]
机构
[1] Univ Arizona, Coll Med, Arizona Resp Ctr, Tucson, AZ 85721 USA
[2] Univ Arizona, Inst BIO5, Tucson, AZ USA
基金
美国国家卫生研究院;
关键词
INNATE IMMUNE-RESPONSE; LUNG-FUNCTION DECLINE; KILLER T-CELLS; NKT CELLS; INTERFERON-GAMMA; RISK-FACTORS; RECEPTOR; IDENTIFICATION; POPULATION; EXPRESSION;
D O I
10.1038/mi.2010.13
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Asthma exacerbations are associated with subsequent deficits in lung function. Here, we tested the hypothesis that a specific pattern of inflammatory responses during acute exacerbations may be associated with chronic airway obstruction. Gene coexpression networks were characterized in induced sputum obtained during an acute exacerbation, from asthmatic children with or without chronic airflow limitation. The data showed that activation of Th1-like/cytotoxic and interferon signaling pathways during acute exacerbations was decreased in asthmatic children with deficits in baseline lung function. These associations were independent of the identification of picornaviruses in nasal secretions or the use of medications at the time of the exacerbation. Th2-related pathways were also detected in the responses, but variations in these pathways were not related to chronic airways obstruction. Our findings show that decreased activation of Th1-like/cytotoxic and interferon pathways is a hallmark of acute exacerbation responses in asthmatic children with evidence of chronic airways obstruction.
引用
收藏
页码:399 / 409
页数:11
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[1]   CD4+ invariant T-cell-receptor plus natural killer T cells in bronchial asthma. [J].
Akbari, O ;
Faul, JL ;
Hoyte, EG ;
Berry, GJ ;
Wahlström, J ;
Kronenberg, M ;
DeKruyff, RH ;
Umetsu, DT .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (11) :1117-1129
[2]   Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity [J].
Akbari, O ;
Stock, P ;
Meyer, E ;
Kronenberg, M ;
Sidobre, S ;
Nakayama, T ;
Taniguchi, M ;
Grusby, MJ ;
DeKruyff, RH ;
Umetsu, DT .
NATURE MEDICINE, 2003, 9 (05) :582-588
[3]   Severe exacerbations predict excess lung function decline in asthma [J].
Bai, T. R. ;
Vonk, J. M. ;
Postma, D. S. ;
Boezen, H. M. .
EUROPEAN RESPIRATORY JOURNAL, 2007, 30 (03) :452-456
[4]   Activation of the granzyme pathway in children with severe respiratory syncytial virus infection [J].
Bem, Reinout A. ;
Bos, Albert P. ;
Bots, Michael ;
Wolbink, Angela M. ;
Van Ham, S. Marieke ;
Medema, Jan Paul ;
Lutter, Rene ;
Van Woensel, Job B. M. .
PEDIATRIC RESEARCH, 2008, 63 (06) :650-655
[5]   Natural killer cells in antiviral defense: Function and regulation by innate cytokines [J].
Biron, CA ;
Nguyen, KB ;
Pien, GC ;
Cousens, LP ;
Salazar-Mather, TP .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :189-220
[6]   A Network Modeling Approach to Analysis of the Th2 Memory Responses Underlying Human Atopic Disease [J].
Bosco, Anthony ;
McKenna, Kathy L. ;
Firth, Martin J. ;
Sly, Peter D. ;
Holt, Patrick G. .
JOURNAL OF IMMUNOLOGY, 2009, 182 (10) :6011-6021
[7]   Conserved and heterogeneous lipid antigen specificities of CD1d-restricted NKT cell receptors [J].
Brigl, Manfred ;
van den Elzen, Peter ;
Chen, Xiuxu ;
Meyers, Jennifer Hartt ;
Wu, Douglass ;
Wong, Chi-Huey ;
Reddington, Faye ;
Illarianov, Petr A. ;
Besra, Gurdyal S. ;
Brenner, Michael B. ;
Gumperz, Jenny E. .
JOURNAL OF IMMUNOLOGY, 2006, 176 (06) :3625-3634
[8]   Rhinovirus-induced interferon-γ and airway responsiveness in asthma [J].
Brooks, GD ;
Buchta, KA ;
Swenson, CA ;
Gern, JE ;
Busse, WW .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 168 (09) :1091-1094
[9]  
*CHILDH ASTHM MAN, 2000, NEW ENGLAND J MED, V0343
[10]   Antigen Presentation by CD1: Lipids, T Cells, and NKT Celts in Microbial Immunity [J].
Cohen, Nadia R. ;
Garg, Salil ;
Brenner, Michael B. .
ADVANCES IN IMMUNOLOGY, VOL 102, 2009, 102 :1-94