Clues as to why some individuals develop severe allergic asthma are presented in a report published this week in Nature Immunology.
Why asthma patients with more severe disease have higher numbers of neutrophils―a type of immune cell―in their lungs exhibit was previously unclear. Marsha Wills-Karp and colleagues have discovered some mice strains develop more severe asthma compared to others and this increase is associated with neutrophil infiltration. The authors found that mice with more severe disease express more interleukin 17 (IL-17) and IL-23―inflammatory molecules linked to neutrophil recruitment and activation.
They also noted that strain differences in IL-17 and IL-23 production were surprisingly attributed to an ancient antimicrobial pathway called complement. Complement activation involves activation of proteases that sequentially release alarm molecules C3a followed by C5a and triggers other immune responses. Wills-Karp and her team find reciprocal regulation by C3a and C5a effects the production of both interleukins, with C3a activating more severe disease and C5a protecting against it.
This new work suggests new therapeutic angles to lessen the severity of neutrophil-dominated forms of asthma.