Lack of WDFY4 Aggravates Ovalbumin-Induced Asthma via Enhanced Th2 Cell Differentiation
Yan Li, Anran Wang, Long Feng, Fei Gao, Shang Gao, Shijun Wei, Liu Ai, Xi Li, Wenjie Sun, Jiangxia Li, Qiji Liu
Abstract
<b><i>Background:</i></b> Asthma is a chronic inflammatory airway disease, and Th2 cells play an important role in asthma. <i>WDFY4</i> (WDFY family member 4) is a susceptibility gene in several autoimmune diseases. <b><i>Objective:</i></b> In this study, the roles of WDFY4 in Th2 cell differentiation and Th2-dependent asthma were investigated. <b><i>Methods:</i></b> Naïve CD4<sup>+</sup> T cells were isolated from wild-type and WDFY4-deficient mice and induced to differentiate in vitro. Subsequently, a mouse model of asthma was established by sensitization with ovalbumin. <b><i>Results:</i></b> Study results showed that WDFY4 deficiency could promote the differentiation of Th2 cells and the production of Th2 cytokines. WDFY4-deficient asthmatic mice showed higher levels of Th2 cytokines in the lungs and bronchoalveolar lavage fluid than wild-type mice. Moreover, infiltration of inflammatory cells, hyperplasia of goblet cells, production of mucus, and deposition of collagen were enhanced in WDFY4-deficient asthmatic mice. <b><i>Conclusions:</i></b> Our study demonstrates the pivotal role of WDFY4 in the pathogenesis of asthma and in Th2 cell differentiation.