Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma

被引:301
作者
Karp, CL
Grupe, A
Schadt, E
Ewart, SL
Keane-Moore, M
Cuomo, PJ
Köhl, J
Wahl, L
Kuperman, D
Germer, S
Aud, D
Peltz, G
Wills-Karp, M
机构
[1] Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[3] Roche Biosci, Palo Alto, CA 94304 USA
[4] Michigan State Univ, Dept Large Anim Sci, E Lansing, MI 48824 USA
[5] Hannover Med Sch, Inst Med Microbiol, D-30625 Hannover, Germany
[6] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA
[7] Roche Mol Syst Inc, Alameda, CA 94501 USA
关键词
D O I
10.1038/79759
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The prevalence and severity of allergic asthma continue to rise, lending urgency to the search for environmental triggers and genetic substrates. Using microarray analysis of pulmonary gene expression and single nucleotide polymorphism-based genotyping, combined with quantitative trait locus analysis, we identified the gene encoding complement factor 5 (CS) as a susceptibility locus for allergen-induced airway hyperresponsiveness in a murine model of asthma. A deletion in the coding sequence of CS leads to C5-deficiency and susceptibility. Interleukin 12 (IL-12) is able to prevent or reverse experimental allergic asthma. Blockade of the C5a receptor rendered human monocytes unable to produce IL-12, mimicking blunted IL-12 production by macrophages from C5-deficient mice and providing a mechanism for the regulation of susceptibility to asthma by C5. The role of complement in modulating susceptibility to asthma highlights the importance of immunoregulatory events at the interface of innate and adaptive immunity in disease pathogenesis.
引用
收藏
页码:221 / 226
页数:6
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