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

Christopher L. Karp, Andrew Grupe, Eric Schadt, Susan L. Ewart, Michelle Keane-Moore, Peter J. Cuomo, Jörg Köhl, Larry Wahl, Douglas Kuperman, Soren Germer, Dee Aud, Gary Peltz, Marsha Wills-Karp

Research output: Contribution to journalArticle

Abstract

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 (C5) as a susceptibility locus for allergen-induced airway hyperresponsiveness in a murine model of asthma. A deletion in the coding sequence of C5 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.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalNature Immunology
Volume1
Issue number3
DOIs
StatePublished - Sep 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Karp, C. L., Grupe, A., Schadt, E., Ewart, S. L., Keane-Moore, M., Cuomo, P. J., Köhl, J., Wahl, L., Kuperman, D., Germer, S., Aud, D., Peltz, G., & Wills-Karp, M. (2000). Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma. Nature Immunology, 1(3), 221-226. https://doi.org/10.1038/79759