Deficiency of Thymic Stromal Lymphopoietin (TSLP) Receptor Signaling Reduced IL-33 Protein Expression and the Number of Lung Group 2 Innate Lymphoid Cells (ILC2) Following Alternaria Extract-Challenge

Abstract

FEBRUARY 2015 AB82 Abstracts S A T U R D A Y 262 Deficiency of Thymic Stromal Lymphopoietin (TSLP) Receptor Signaling Reduced IL-33 Protein Expression and the Number of Lung Group 2 Innate Lymphoid Cells (ILC2) Following Alternaria Extract-Challenge Shinji Toki, PhD, Kasia Goleniewska, Sara Reiss, MS, Baohua Zhou, PhD, R. Stokes Peebles, Jr, MD, FAAAAI; Vanderbilt University School of Medicine, Nashville, TN, Indiana University School of Medicine, Indianapolis, IN. RATIONALE: TSLP has a critical role in the development of allergic inflammation in mice. It has been reported that TSLP synergistically promoted the number and Th2 cytokine production of IL-33-induced ILC2 in vitro; however, whether TSLP regulates IL-33 expression is unknown. We hypothesized that TSLP regulates IL-33 protein expression and the number of ILC2 in the lung following allergen challenge. To test this hypothesis, we evaluated IL-33 protein expression and the number of ILC2 in the lung by using WT and TSLP receptor deficient (TSLPR) mice following Alternaria extract-challenge. METHODS: BALB/c background WT and TSLPRmice were intranasally challenged with Alternaria extract for 4 consecutive days. Bronchoalveolar lavage (BAL) fluids and lungs were harvested 24 hours after the last challenge. Control mice were challenged with PBS. IL-33, IL-5 and IL-13 protein level in the BAL fluid and lung homogenate were measured by ELISA. Eosinophils in the BAL fluids were counted after Wright-Giemsa staining. ILC2 in the lungs were detected by flow cytometry. RESULTS: TSLPR mice had significantly decreased lung IL-33 protein and ILC2 following Alternaria-challenge compared to WTmice (p<0.05). Further, the number of eosinophils and the protein level of IL-5 and IL-13 were also significantly decreased in BAL fluid of TSLPR mice compared to WT mice (p<0.05). CONCLUSIONS: TSLPR signaling is necessary for the full expression of lung IL-33 protein expression following allergen challenge. TSLPR signaling also promotes the number of allergen-induced lung ILC2.