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Review
. 2016 Aug;117(2):108-14.
doi: 10.1016/j.anai.2016.04.022.

The immunology of asthma: Asthma phenotypes and their implications for personalized treatment

Larry Borish  1
Affiliations
Review

The immunology of asthma: Asthma phenotypes and their implications for personalized treatment

Larry Borish. Ann Allergy Asthma Immunol. 2016 Aug.

Abstract

Objectives: To review current thinking regarding the role of personalized phenotype-driven as opposed to broad guideline-based therapies in asthma and to speculate on the relative contributions of innate (lung) and adaptive (T and B lymphocyte) roles in asthma pathogenesis.

Data sources: PubMed literature review.

Study selections: Articles pertaining to asthma pathogenesis, with emphasis on those that included biotherapeutic interventions.

Results: Current methods allow asthma to be divided into phenotypes characterized by the presence or absence of eosinophilic inflammation. Corticosteroids are likely to be only effective in the context of eosinophilic inflammation. Similarly, interventions with biotherapeutic agents currently available or in development have efficacious only when administered to patients with asthma of relevant phenotypes.

Conclusion: The availability of biotherapeutic agents that target IgE, interleukin (IL) 5, and, in the near future, IL-13 is an exciting vindication of molecular medicine. However, these biotherapeutic agents are only effective when targeted to patients with specific asthma phenotypes. In Promising biotherapeutic targets are the airway epithelial-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin. Targeting these lung epithelial-derived mediators, instead of products of the adaptive immune system, may be more likely to improve day-to-day asthma symptoms in contrast to agents that target the adaptive immune system, approaches that primarily act to ameliorate asthma exacerbations.

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Figures

Figure 1
Figure 1
Responsiveness of Th2 high asthma to inhaled steroids. FEV1 at baseline, after 4 and 8 weeks on fluticasone (500 µg BID), and 1 week after the cessation of fluticasone (week 9) according to cohort. Reproduced with permission from.
Figure 2
Figure 2
Airway epithelial cell contribution to type 2 inflammation in asthma. Figure 2a. Epithelial cell derived IL-25, IL-33, and TSLP drive differentiation of Th2 effector cells via either direct influence on naïve T cells (IL-25 and IL-33) or influencing the function of antigen-presenting DCs (TSLP). Figure 2b. Once expressed, these cytokines do not require T effector lymphocytes to produce this type 2 cytokine milieu and can drive IL-4, IL-5, IL-9, and IL-13 secretion from ILC2s and eosinophils. Figure 2c. Other cytokines and chemokines produced by these epigenetically-modified epithelial cells drive eosinophil recruitment and activation, again without the need for allergen-dependent Th2 lymphocytes.
Figure 2
Figure 2
Airway epithelial cell contribution to type 2 inflammation in asthma. Figure 2a. Epithelial cell derived IL-25, IL-33, and TSLP drive differentiation of Th2 effector cells via either direct influence on naïve T cells (IL-25 and IL-33) or influencing the function of antigen-presenting DCs (TSLP). Figure 2b. Once expressed, these cytokines do not require T effector lymphocytes to produce this type 2 cytokine milieu and can drive IL-4, IL-5, IL-9, and IL-13 secretion from ILC2s and eosinophils. Figure 2c. Other cytokines and chemokines produced by these epigenetically-modified epithelial cells drive eosinophil recruitment and activation, again without the need for allergen-dependent Th2 lymphocytes.
Figure 2
Figure 2
Airway epithelial cell contribution to type 2 inflammation in asthma. Figure 2a. Epithelial cell derived IL-25, IL-33, and TSLP drive differentiation of Th2 effector cells via either direct influence on naïve T cells (IL-25 and IL-33) or influencing the function of antigen-presenting DCs (TSLP). Figure 2b. Once expressed, these cytokines do not require T effector lymphocytes to produce this type 2 cytokine milieu and can drive IL-4, IL-5, IL-9, and IL-13 secretion from ILC2s and eosinophils. Figure 2c. Other cytokines and chemokines produced by these epigenetically-modified epithelial cells drive eosinophil recruitment and activation, again without the need for allergen-dependent Th2 lymphocytes.
Figure 3
Figure 3
Model of roles of innate and adaptive immunity in asthma. See text for details.
See this image and copyright information in PMC

References

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