Ex vivo air-liquid interface respiratory mucosa platform to study type 2-driven asthma.

Area of Science:

• Immunology
• Respiratory Medicine
• 3D Tissue Models

Background:

• Asthma is a complex respiratory disease with a type 2 (T2-high) inflammatory endotype.
• Existing animal and 2D cell models fail to fully replicate human airway immune responses, especially the T2-high phenotype.

Purpose of the Study:

• To develop a novel 3D ex vivo human nasal mucosa model.
• To incorporate type-2-biased immune stimulation for studying T2-high airway inflammation.

Main Methods:

• Expanded primary human nasal mucosal biopsies under air-liquid interface (ALI) conditions.
• Stimulated tissues with IL-4/IL-13 or co-cultured with autologous Th2 lymphocytes and dendritic cells.
• Monitored tissue morphology, barrier function (TEER), and inflammatory marker secretion.

Main Results:

• Successfully induced a T2-high inflammatory state, confirmed by increased periostin, STAT-6, IL-4, and IL-13 secretion.
• Observed modest TEER reduction and epithelial remodeling, characteristic of T2-high inflammation.
• Exclusion of COPD-like or T2-low phenotypes based on stable IL-8 and chitinase protein levels.

Conclusions:

• The developed 3D ex vivo model effectively reproduces key immunopathologic features of T2-high airway inflammation in a human-relevant context.
• This model serves as a stable platform for mechanistic investigations and preclinical screening of targeted anti-inflammatory therapies for asthma.