Lack of WDFY4 Aggravates Ovalbumin-Induced Asthma via Enhanced Th2 Cell Differentiation

Int Arch Allergy Immunol. 2021;182(11):1089-1096. doi: 10.1159/000516970. Epub 2021 Aug 23.

Abstract

Background: Asthma is a chronic inflammatory airway disease, and Th2 cells play an important role in asthma. WDFY4 (WDFY family member 4) is a susceptibility gene in several autoimmune diseases.

Objective: In this study, the roles of WDFY4 in Th2 cell differentiation and Th2-dependent asthma were investigated.

Methods: Naïve CD4+ 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.

Results: 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.

Conclusions: Our study demonstrates the pivotal role of WDFY4 in the pathogenesis of asthma and in Th2 cell differentiation.

Keywords: Asthma; Th2 cell; WDFY4.

MeSH terms

  • Airway Remodeling
  • Allergens / immunology
  • Animals
  • Asthma / immunology*
  • Asthma / pathology
  • Cell Differentiation
  • Cytokines / genetics
  • Cytokines / immunology
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Th2 Cells / immunology*

Substances

  • Allergens
  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Wdfy4 protein, mouse
  • Ovalbumin