Allergen-induced asthma, chronic rhinosinusitis and transforming growth factor-β superfamily signaling: mechanisms and functional consequences

Expert Rev Clin Immunol. 2019 Nov;15(11):1155-1170. doi: 10.1080/1744666X.2020.1672538. Epub 2019 Oct 19.

Abstract

Introduction: Often co-associated, asthma and chronic rhinosinusitis (CRS) are complex heterogeneous disease syndromes. Severity in both is related to tissue inflammation and abnormal repair (termed remodeling). Understanding signaling factors that can modulate, integrate the activation, and regulation of such key processes together is increasingly important. The transforming growth factor (TGF)-β superfamily of ligands comprise a versatile system of immunomodulatory molecules that are gaining recognition as having an essential function in the immunopathogenesis of asthma. Early data suggest an important role in CRS as well. Abnormal or dysregulated signaling may contribute to disease pathogenesis and severity.Areas covered: The essential biology of this complex family of growth factors in relation to the excess inflammation and remodeling that occurs in allergic asthma and CRS is reviewed. The need to understand the integration of signaling pathways together is highlighted. Studies in human airway tissue are evaluated and only selected key animal models relevant to human disease discussed given the highly context-dependent signaling and function of these ligands.Expert opinion: Abnormal or dysregulated TGF-β superfamily signaling may be central to the excess inflammation and tissue remodeling in asthma, and possibly CRS. Therefore, the TGF-β superfamily signaling pathways represent an emerging and attractive therapeutic target.

Keywords: Asthma; TGF-β superfamily; chronic rhinosinusitis; immune dysregulation; immunopathogenesis; inflammation; remodeling.

Publication types

  • Review
  • Video-Audio Media

MeSH terms

  • Animals
  • Asthma / immunology*
  • Asthma / pathology
  • Chronic Disease
  • Humans
  • Multigene Family / immunology*
  • Rhinitis, Allergic / immunology*
  • Rhinitis, Allergic / pathology
  • Signal Transduction / immunology*
  • Sinusitis / immunology*
  • Sinusitis / pathology
  • Transforming Growth Factor beta / immunology*

Substances

  • Transforming Growth Factor beta