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

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
• chronic rhinosinusitis
• immunopathogenesis
• immune dysregulation
• inflammation
• remodeling
• TGF-β superfamily

Article highlights

• TGF-β superfamily signaling is complex and current studies on airway disease are limited but suggest altered signaling pathways and therefore a dysregulated system is present. Such aberrant signaling likely contributes to the excess inflammation and remodeling seen in allergic asthma and CRS.

• Ligand signaling in asthma is rapid and not standalone but appears to be integrated and modulated in a complex time-course manner.

• Further studies using better models of disease harnessing emerging tissue engineering methods and single-cell technology are needed to further understand the integrated functional context and cell-specific multiple signaling pathways together in both health and disease. Only then can safe therapeutic strategies that can harness such powerful immune-modulatory growth factors to promote simultaneous inflammatory regulation and tissue repair be considered.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.