Prolonged allergen exposure is associated with increased thymic stromal lymphopoietin expression and Th2-skewing in mouse models of chronic rhinosinusitis

Abstract

Objectives/hypothesis: Chronic rhinosinusitis (CRS) is characterized by a dysfunctional host-environment interaction at the nasal mucosa. Contributions of host susceptibility factors such as atopy and aspirin sensitivity to CRS pathophysiology are well established. However, clinical studies on the effects of environmental factors are limited. This study investigates the histological and immunological effects of allergen exposure duration in animal models.

Study design: Animal study.

Methods: A murine model for CRS with nasal polypoid lesions was induced by instilling ovalbumin/staphylococcal enterotoxin B (SEB) into murine nasal cavities for 12 (short term) or 24 weeks (long term). Histopathological changes were observed. Interleukin (IL)-4, IL-17A, IL-10, and interferon (INF)-γ levels from nasal lavage fluid were measured using enzyme-linked immunosorbent assay. Gene expressions of IL-25, thymic stromal lymphopoietin (TSLP), IL-4, IL-5, INF-γ, C-C motif chemokine ligand (CCL)-11, CCL-24, C-X-C motif chemokine ligand (CXCL)-1, CXCL-2, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, matrix metallopeptidase (MMP)-7, and tissue inhibitor of metalloproteinase (TIMP)-3 were analyzed from the nasal mucosa.

Results: Long-term CRS models exhibited increased polypoid lesions, edematous mucosal thickness, and eosinophil infiltration compared with short-term models and showed a higher IL-10 level but lower IFN-γ and IL-17A protein levels. Moreover, CCL-24 and MMP-7 gene expressions increased whereas TIMP-3 expression decreased in long-term models compared to controls and short-term models. IL-25 and TSLP expressions were upregulated at mRNA and protein levels in short-term and long-term CRS models, respectively. Furthermore, TSLP mRNA expression was positively associated with IL-5 (r = 0.8754) and inversely correlated to IFN-γ (r = -0.7212) in CRS models.

Conclusions: Prolonged allergen exposure in ovalbumin/SEB-induced CRS models maintains Th2 inflammation and reduces Th1 inflammation, which was associated with upregulation of TSLP.

Level of evidence: NA Laryngoscope, 126:E265-E272, 2016.

Keywords: Animal model; eosinophil; nasal polyps; rhinosinusitis; thymic stromal lymphopoietin.