Cell-Specific Role of IL4Rα Signaling in Allergic Asthma

Author

Ishita Choudhary, Louisiana State University and Agricultural and Mechanical CollegeFollow

Degree

Doctor of Philosophy (PhD)

Department

Comparative Biomedical Sciences

Document Type

Dissertation

Abstract

IL-4 and IL-13 play a critical role in allergic asthma pathogenesis via their common receptor, i.e., interleukin 4 receptor alpha (IL4Rα). However, the cell type-specific role of IL4Rα-mediated signaling in allergic asthma has remained unclear. We hypothesized that the role of IL4Rα signaling in allergic asthma is cell-type specific. To test our hypothesis, we challenged myeloid cell-specific IL4Rα-deficient (LysMcre^+/+/IL4Rα^fl/fl), myeloid cell-specific IL4Rα-sufficient (LysMcre^+/+/IL4Rα^wt/wt), airway epithelial cell-specific IL4Rα-deficient (CCSP-Cre⁺/IL4Rα^fl/fl), and airway epithelial cell-specific IL4Rα-sufficient (CCSP-Cre^-/IL4Rα^fl/fl) mice with either mixed allergens (MA) or normal saline three times a week for four weeks and examined the lung phenotypes 24 hrs. post-last MA/ normal saline dose. In contrast to MA-challenged myeloid cell-specific IL4Rα-sufficient mice, myeloid cell-specific IL4Rα-deficient mice showed decrease in eosinophils and lymphocytes recruitment, production of Th2 cytokines and chemokines, airway hyperresponsiveness, IgE antibody production, subepithelial fibrosis, and inflammatory lung pathology. Airway epithelial cell-specific IL4Rα-deficient mice, on the other hand, exhibited diminished MA-induced mucous cell metaplasia (MCM) and mucins production as compared to airway epithelial cell-specific IL4Rα-sufficient mice. Taken together, our data show that in MA-induced allergic asthma model, myeloid cell-specific IL4Rα signaling is critically required for eosinophil and lymphocyte recruitment, production of Th2 cytokines and chemokines, airway hyperresponsiveness, IgE antibody production, subepithelial fibrosis, and inflammatory lung pathology while airway epithelial cell-specific IL4Rα signaling is critically required for MCM and mucins production.

Date

4-7-2023

Recommended Citation

Choudhary, Ishita, "Cell-Specific Role of IL4Rα Signaling in Allergic Asthma" (2023). LSU Doctoral Dissertations. 6084.
https://repository.lsu.edu/gradschool_dissertations/6084

Committee Chair

Saini, Yogesh

DOI

10.31390/gradschool_dissertations.6084