Abstract Rationale Fibrosis involves complex cellular and molecular interactions leading to organ dysfunction and significant impacts on quality of life. Among the signalling pathways implicated, the chemokine CXCL12 and its receptor CXCR4 have been associated with fibrotic diseases of the lung, liver, and skin. Our previous work demonstrated that elevated CXCL12 levels mobilize mesenchymal stromal cell migration into the airway smooth muscle, contributing to the pathophysiology of airway diseases such as asthma. To optimise therapeutic targeting of this pathway, further characterisation of CXCL12 expression and regulation is required. Methods To investigate changes CXCL12 production in asthmatic airways, we analysed lung tissue from mice exposed to house dust mite (HDM) for 5 days/week for 7 weeks. Lungs were harvested, frozen, and sectioned for immunostaining with anti-CXCL12 and anti-α-smooth muscle actin (α-SMA) antibodies, followed by confocal microscopy. To further validate these findings, air-liquid interface (ALI) cultures of human bronchial epithelial cells were established on 0.4 µm Transwell inserts. Following barrier formation, cells were differentiated and exposed to HDM extract (ranging from 12.5 mg to 50 mg per well) to induce epithelial damage, with bovine serum albumin (BSA) serving as a negative control. Cultures were analysed by brightfield and immunofluorescence microscopy. Results In mouse lung sections, CXCL12 was localised predominantly in airway epithelial cells, with more robust expression observed following HDM exposure. ALI cultures exhibited characteristic differentiation features, including cilia and mucus formation. HDM challenge resulted in a dose-dependent increase in CXCL12 expression compared with untreated controls. Conclusions These findings indicate that airway epithelial cells are a key source of CXCL12 in response to allergen-induced damage. This localisation identifies a potential target site for therapeutic intervention and supports the feasibility of topical drug delivery via inhalation to modulate the CXCL12-CXCR4 axis in chronic allergic airway disease in an effort to mitigate airway smooth muscle thickening. This abstract is funded by: BBSRC Innovation Accelerator
Johnson et al. (Fri,) studied this question.