Clinical view on the importance of dendritic cells in asthma

Abstract

Allergic asthma is characterized by airway hyperresponsiveness and inflammation and may lead to airway remodeling in uncontrolled cases. Genetic predisposition to an atopic phenotype plays a major component in the pathophysiology of asthma. However, with tremendous role of epigenetic factors and environmental stimuli in precipitating an immune response, the underlying pathophysiological mechanisms are complicated. Dendritic cells are principal antigen-presenting cells and initiators of the immune response in allergic asthma. Their phenotype, guided by multiple factors may dictate the immune reaction to an allergic or tolerogenic response. Involvement of the local cytokine milieu, microbiome and interplay between immune cells add dimension to the fate of immune response. In addition to allergen exposure, these factors modulate DC phenotype and function. In this article, integration of many factors and pathways associated with the recruitment and activation of DCs in the pathophysiology of allergic asthma is presented in a clinical and translational manner.

Keywords::

• allergic asthma
• antigen tolerance dendritic cell
• microbiome

Financial & competing interests disclosure

This work was supported by NIH grants to DK Agrawal. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The content of this review is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Phenotype of dendritic cells (DCs) may determine the type of immune reaction generated in response to allergen.

• • Genetic, epigenetic and environmental factors dictate differentiation and maturation of a specific DC phenotype.

• • Different types of antigens are recognized through pattern recognition receptors on DCs for immune precipitation to allergy or tolerance.

• • Local microbiome can change the immune polarization to atopic or tolerogenic response through DCs.

• • Environmental exposure of pollutants and reactive oxygen species, including free radicals, may modulate the activation of DCs to generate an allergic response on exposure to allergens.

• • Target therapy with tailored allergens and microorganisms, recognized by DCs to favor Th1 or Tregs, can ameliorate allergic asthma.

Notes