Regulation of chronic lung inflammation to house dust mite allergen by Wnt antagonist (CAM1P.144)

• Published in: The Journal of immunology (1950) Vol. 194; no. 1_Supplement; pp. 48 - 48.1
• Main Authors: Bothwell, Alfred, Chae, WookJin, Teixeira, Alexandra, Chan, Pamela, Hao, Liming, Rothlin, Carla, Krause, Diane
• Format: Journal Article
• Language: English
• Published: 01-05-2015
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.194.Supp.48.1

Recruitment of leukocytes in response to allergen is an important step in the initiation of airway inflammation. Here we demonstrate that the Wnt antagonist Dkk-1 regulates the formation of leukocyte-platelet aggregates (LPAs) following house dust mite (HDM) allergen challenge. We show that circulating Dkk-1 is elevated after recurrent HDM allergen challenges and the source is activated platelets. The increase of P-selectin glycoprotein ligand-1 (PSGL-1) expression in leukocytes was mediated by Dkk-1 while other cell adhesion molecules such as ICAM-1 or LFA-1 were only marginally affected. The formation of LPAs was markedly reduced in Dkk-1 hypomorphic doubleridge (Dkk-1d/d) mice that had a 90% reduction of circulating Dkk-1. Recurrent allergen challenges in Dkk-1d/d mice showed significantly reduced infiltration of leukocytes including neutrophils in the lung compared to wildtype mice. Importantly, we show that type 2 cytokines (e.g. IL-4, IL-5 and IL-13) from CD4 T cells in mediastinal lymph nodes (med LNs) of Dkk-1d/d mice were substantially reduced compared to wildtype mice following allergen exposure. Consistently, we observed Gata-3 and c-Maf induction in Th2 cells did not occur in med LN CD4 T cells from Dkk-1d/d mice. Therefore, our results demonstrate that the Wnt antagonist from activated platelets regulates the early stage of leukocyte infiltration in the challenged tissue, thereby regulating inflammation and type 2 immune responses.