MONDAY, Aug. 30 (HealthDay News) -- Interleukin-17A (IL-17A) has been identified as a promoter of severe asthma-like symptoms in mice, a finding that may provide a basis for further research into therapeutic treatments for severe asthma in humans, according to research published online Aug. 29 in Nature Immunology.
To determine the role of IL-17A in severe asthma and ascertain the factors that drive its production, Stephane Lajoie, Ph.D., of the University of Cincinnati College of Medicine, and colleagues examined mice genetically bred to resemble humans susceptible to severe asthma.
The researchers found that mice deficient in the C5 gene generated large numbers of IL-17-producing helper T (TH17) cells, resulting in significant IL-17A production and airway hyper-responsiveness. Blocking IL-17A production in these mice reduced airway hyper-responsiveness. Mice deficient in C3aR genes had fewer TH17 cells and also less airway hyper-responsiveness; an increase in IL-17A in the airways of these mice resulted in greater airway hyper-responsiveness. The authors write that reciprocal regulation of IL-23 production mediated C3a's and C5a's opposing effects.
"As severe forms of asthma have proven difficult to treat with existing therapies, modulation of anaphylatoxins may hold promise for the treatment of this ever-increasing disease. Our findings have implications beyond the context of asthma, as in both mice and humans, the dysregulation of complement pathways has been linked to a plethora of chronic inflammatory human diseases in which IL-17A has an important role," the authors conclude.
One study author is an employee of Amgen.
Abstract
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