Identification of innate immune response endotypes in asthma: Implications for personalized medicine

Allan R. Brasier

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Asthma is an idiopathic disease characterized by episodic inflammation and reversible airway obstruction triggered by exposure to environmental agents. Because this disease is heterogeneous in onset, exacerbations, inflammatory states, and response to therapy, there is intense interest in developing personalized approaches to its management. Of focus in this review, the recognition that a component of the pathophysiology of asthma is mediated by inflammation has implications for understanding its etiology and individualizing its therapy. Despite understanding how Th2 polarization mediates asthma exacerbations by aeroallergen exposure, we do not yet fully understand how RNA virus infections produce asthmatic exacerbations. This review will summarize the explosion of information that has revealed how patterns produced by RNA virus infection trigger the innate immune response (IIR) in sentinel airway cells. When the IIR is triggered, these cells elaborate inflammatory cytokines and protective mucosal interferons whose actions activate long-lived adaptive immunity and limit organismal replication. Recent work has shown the multifaceted way that dysregulation of the IIR is linked to viral-induced exacerbation, steroid insensitivity, and T helper polarization of adaptive immunity. New developments in quantitative proteomics now enable accurate identification of subgroups of individuals that demonstrate activation of IIR ("innate endotype"). Potential applications to clinical research are proposed. Together, these developments open realistic prospects for how identification of the IIR endotype may inform asthma therapy in the future.

Original languageEnglish (US)
Pages (from-to)462-468
Number of pages7
JournalCurrent Allergy and Asthma Reports
Volume13
Issue number5
DOIs
StatePublished - Oct 2013

Keywords

  • Asthma
  • Endotypes
  • Innate immune response (IIR)
  • Innate immune response endotypes
  • Interferon (IFN)
  • Interferon response factor (IRF)
  • Multivariate adaptive regression splines
  • Nuclear factor-κB (NFκB)
  • Pattern recognition receptors
  • Personalized medicine
  • Respiratory syncytial virus
  • Retinoic acid like helicases (RLH)
  • Toll-like receptors (TLRs)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

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