New perspectives on the regulation of type II inflammation in asthma

Mireya Becerra-Díaz, Marsha Wills-Karp, Nicola M. Heller

Research output: Contribution to journalReview article

Abstract

Asthma is a chronic inflammatory disease of the lungs which has been thought to arise as a result of inappropriately directed T helper type-2 (Th2) immune responses of the lungs to otherwise innocuous inhaled antigens. Current asthma therapeutics are directed towards the amelioration of downstream consequences of type-2 immune responses (i.e. β-agonists) or broad-spectrum immunosuppression (i.e. corticosteroids). However, few approaches to date have been focused on the primary prevention of immune deviation. Advances in molecular phenotyping reveal heterogeneity within the asthmatic population with multiple endotypes whose varying expression depends on the interplay between numerous environmental factors and the inheritance of a broad range of susceptibility genes. The most common endotype is one described as "type-2-high" (i.e. high levels of interleukin [IL]-13, eosinophilia, and periostin). The identification of multiple endotypes has provided a potential explanation for the observations that therapies directed at typical Th2 cytokines (IL-4, IL-5, and IL-13) and their receptors have often fallen short when they were tested in a diverse group of asthmatic patients without first stratifying based on disease endotype or severity. However, despite the incorporation of endotype-dependent stratification schemes into clinical trial designs, variation in drug responses are still apparent, suggesting that additional genetic/environmental factors may be contributing to the diversity in drug efficacy. Herein, we will review recent advances in our understanding of the complex pathways involved in the initiation and regulation of type-2-mediated immune responses and their modulation by host factors (genetics, metabolic status, and the microbiome). Particular consideration will be given to how this knowledge could pave the way for further refinement of disease endotypes and/or the development of novel therapeutic strategies for the treatment of asthma.

Original languageEnglish (US)
Article number1014
JournalF1000Research
Volume6
DOIs
StatePublished - 2017

Fingerprint

Asthma
Inflammation
Supravalvular Aortic Stenosis
Lung
Cyclic AMP Receptor Protein
Modulation
Interleukin-13 Receptors
Interleukin-13
Microbiota
Interleukin-5
Eosinophilia
Primary Prevention
Interleukin-4
Immunosuppression
Adrenal Cortex Hormones
Chronic Disease
Clinical Trials
Cytokines
Antigens
Genes

Keywords

  • Alarmins
  • Allergic inflammation
  • Asthma
  • Cellular metabolism
  • Cytokines
  • Signalling
  • Th2 inflammation

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

New perspectives on the regulation of type II inflammation in asthma. / Becerra-Díaz, Mireya; Wills-Karp, Marsha; Heller, Nicola M.

In: F1000Research, Vol. 6, 1014, 2017.

Research output: Contribution to journalReview article

Becerra-Díaz, Mireya; Wills-Karp, Marsha; Heller, Nicola M. / New perspectives on the regulation of type II inflammation in asthma.

In: F1000Research, Vol. 6, 1014, 2017.

Research output: Contribution to journalReview article

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