Prolonged Allergen Exposure Causes TSLP-Mediated Th2-Skewing in Mouse Models of Chronic Rhinosinusitis
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Dong-Kyu Kim, MD, Kyung Mi Eun, Hong Ryul Jin, MD, Seong Ho Cho, MD FAAAAI, Dae Woo Kim, MD
Rationale: 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.

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-5, INF-γ, CCL11, CCL24, ICAM-1, VCAM-1, MMP7, and TIMP3 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-4/IFN-γ ratio and IL-10 level but lower IFN-γ and IL-17A protein levels. Moreover, CCL24 and MMP7 gene expressions increased whereas TIMP3 expression decreased in longterm models compared to controls and short-term models. Epithelium-derived IL-25 and TSLP mRNA expressions were up-regulated 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 up-regulation of TSLP.