KIF2A decreases IL-33 production and attenuates allergic asthmatic inflammation

Background: The microtubule-dependent molecular motor protein Kinesin Family Member 2A (KIF2A) is down-regulated in asthmatic human airway epithelium. However, little is known about the roles of KIF2A as well as the possible underlying mechanisms in asthma.

Methods: House dust Mite (HDM) extract was administered to establish a murine model of asthma. The expression of KIF2A, IL-33 and the Autophagy pathways were detected. The plasmid pCMV-KIF2A was used to overexpress KIF2A in the airway epithelial cells in vitro and in vivo. IL-4, IL-5, IL-33 and other cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues homogenates were measured.

Results: In response to the challenge of house dust Mite (HDM) in vitro and in vivo, airway epithelial cells displayed decreased production of KIF2A. Meanwhile, Autophagy and IL-33 were increased in HMD-treated epithelial cells. Mechanistically, KIF2A decreased Autophagy via suppressing mTORC1 pathway in HDM-treated epithelial cells, which contributed to the reduced production of IL-33. Moreover, in vivo KIF2A transfection reduced IL-33 and Autophagy in the lung, leading to the attenuation of allergic asthma.

Conclusion: KIF2A suppressed mTORC1-mediated Autophagy and decreased the production of epithelial-derived cytokine IL-33 in allergic airway inflammation. These data indicate that KIF2A may be a novel target in allergic asthma.