First published September 18, 2017 - More info
Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and a cellular infiltrate dominated by eosinophils. Numerous epidemiological studies have related the exacerbation of allergic asthma with an increase in ambient inhalable particulate matter from air pollutants. This is because inhalable particles efficiently deliver airborne allergens deep into the airways, where they can aggravate allergic asthma symptoms. However, the cellular mechanisms by which inhalable particulate allergens (pAgs) potentiate asthmatic symptoms remain unknown, in part because most in vivo and in vitro studies exploring the pathogenesis of allergic asthma use soluble allergens (sAgs). Using a mouse model of allergic asthma, we found that, compared with their sAg counterparts, pAgs triggered markedly heightened airway hyperresponsiveness and pulmonary eosinophilia in allergen-sensitized mice. Mast cells (MCs) were implicated in this divergent response, as the differences in airway inflammatory responses provoked by the physical nature of the allergens were attenuated in MC-deficient mice. The pAgs were found to mediate MC-dependent responses by enhancing retention of pAg/IgE/FcεRI complexes within lipid raft–enriched, CD63+ endocytic compartments, which prolonged IgE/FcεRI-initiated signaling and resulted in heightened cytokine responses. These results reveal how the physical attributes of allergens can co-opt MC endocytic circuitry and signaling responses to aggravate pathological responses of allergic asthma in mice.
Cong Jin, Christopher P. Shelburne, Guojie Li, Erin N. Potts, Kristina J. Riebe, Gregory D. Sempowski, W. Michael Foster, Soman N. Abraham
Original citation: J Clin Invest. 2011;121(3):941–955. https://doi.org/10.1172/JCI43584
Citation for this expression of concern: J Clin Invest. 2017;127(10):3913. https://doi.org/10.1172/JCI97321
An investigative committee at Duke University recently reported that a research technician in the animal pulmonary physiology laboratory fabricated and/or falsified flexiVent data reported in Figures 1A, 2A, and 7D of this paper. The Editorial Board is issuing this Expression of Concern to alert readers to these problems. The Editors have requested that the experiments in question be repeated by the authors and resubmitted to the Journal. We will inform our readers of the outcome after the data have been evaluated.