Activin-A Is a Pro-Inflammatory Regulator in Type-2-Driven Upper Airway Disease

Area of Science:

• Immunology
• Otorhinolaryngology
• Cell Biology

Background:

• Allergic upper airway diseases involve type-2 cytokines like IL-5 and TGF-β1.
• Activin-A, a TGF-β superfamily member, shares signaling pathways with TGF-β1.
• The coregulation of activin-A and TGF-β1 in the upper airway is not well understood.

Purpose of the Study:

• To investigate the coregulation of mucosal activin-A and TGF-β1 in acute allergic and chronic Th2-driven upper airway diseases.
• To determine the role of activin-A in the context of allergic rhinitis and nasal polyps.

Main Methods:

• Nasal allergen challenges in patients with seasonal allergic rhinitis to assess cytokine expression kinetics via RT-PCR.
• Analysis of mucosal specimens from patients with chronic upper airway disease with nasal polyps using ELISPOTs and confocal microscopy.
• Ex vivo stimulation of nasal mucosa and primary cell cultures to study activin-A and TGF-β1 interactions.

Main Results:

• Mucosal activin-A expression correlated with IL-5 and TGF-β1, significantly upregulating 6 hours post-allergen challenge.
• Elevated activin-A-producing cells (48-fold increase) were observed in nasal polyps, with decreased submucosal signaling.
• Ex vivo studies indicated mutual regulation of activin-A and TGF-β1 mRNA expression, with combined effects enhancing IL-5 production.

Conclusions:

• Activin-A functions as a pro-inflammatory mediator in allergic upper airway disease.
• Activin-A modifies TGF-β1 activity in the upper airways, opposing its anti-inflammatory role seen in lymphatic compartments.