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Review
. 2015:2015:879783.
doi: 10.1155/2015/879783. Epub 2015 Mar 23.

Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma

Girolamo Pelaia  1 , Alessandro Vatrella  2 , Maria Teresa Busceti  1 , Luca Gallelli  3 , Cecilia Calabrese  4 , Rosa Terracciano  3 , Rosario Maselli  1
Affiliations
Review

Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma

Girolamo Pelaia et al. Mediators Inflamm. 2015.

Abstract

Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments.

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Figures

Figure 1
Figure 1
Pathobiology of airway inflammation in asthma. Asthma originates from complex interactions between genetic factors and environmental agents such as aeroallergens and respiratory viruses. In particular, within the airway lumen allergens can be captured by dendritic cells, which process antigenic molecules and present them to naïve (Th0) T helper cells. The consequent activation of allergen-specific Th2 cells is responsible for the production of IL-4 and IL-13 that promote B-cell operated synthesis of IgE antibodies; moreover, Th2 cells also release IL-5, which induces eosinophil maturation and survival. These events are noticeably favoured by a functional defect of IL-10/TGF-β producing T regulatory (Treg) cells that normally exert an immunosuppressive action on Th2 cell-mediated responses. In addition to Th2 cells, IL-9 releasing Th9 cells can also undergo activation, thus leading to the growth and recruitment of mast cells, which upon IgE-dependent degranulation release both preformed and newly synthesized mediators. Other important T lymphocytes contributing to asthma pathobiology are Th17 cells, producing IL17A and IL-17F which cause neutrophil recruitment and expansion. Furthermore, IL-12-dependent and IFN-γ releasing Th1 cells can be activated, especially as a result of airway infections sustained by respiratory viruses. Finally, many mediators, cytokines, and growth factors produced by several different cells involved in chronic asthmatic inflammation may also affect the functions and proliferation rates of airway structural cellular elements including epithelial cells, fibroblasts, smooth muscle cells, and endothelial vascular cells. See text for further details.
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References

    1. Anderson G. P. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. The Lancet. 2008;372(9643):1107–1119. doi: 10.1016/S0140-6736(08)61452-X. - DOI - PubMed
    1. Holgate S. T., Arshad H. S., Roberts G. C., Howarth P. H., Thurner P., Davies D. E. A new look at the pathogenesis of asthma. Clinical Science. 2010;118(7):439–450. doi: 10.1042/CS20090474. - DOI - PMC - PubMed
    1. Anandan C., Nurmatov U., Van Schayck O. C. P., Sheikh A. Is the prevalence of asthma declining? Systematic review of epidemiological studies. Allergy. 2010;65(2):152–167. doi: 10.1111/j.1398-9995.2009.02244.x. - DOI - PubMed
    1. Masoli M., Fabian D., Holt S., Beasley R. The global burden of asthma: executive summary of the GINA dissemination committee report. Allergy. 2004;59(5):469–478. doi: 10.1111/j.1398-9995.2004.00526.x. - DOI - PubMed
    1. Chanez P., Humbert M. Asthma: still a promising future? European Respiratory Review. 2014;23(134):405–407. doi: 10.1183/09059180.00009614. - DOI - PMC - PubMed