4043 Clusterin Modulates Allergic Airway Inflammation By Attenuating CCL20-Mediated Dendritic Cell Recruitment

Saturday, 17 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Gyong Hwa Hong, BS , Asan Institute for Life Sciences, Seoul, South Korea

Hyouk-Soo Kwon, MD, PhD , Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Keun Ai Moon, MS , Asan Institute for Life Sciences, Seoul, South Korea

So Young Park, MD , Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Sunjoo Park, PhD , Asan Institute for Life Sciences, Seoul, South Korea

Kyoung Young Lee, BS , Asan Institute for Life Sciences, Seoul, South Korea

Eun Hee Ha, BS , Asan Institute for Life Sciences, Seoul, South Korea

Tae-Bum Kim, MD, PhD , Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Hee-Bom Moon, MD, PhD , Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

You Sook Cho, MD, PhD , Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Background: Recruitment and activation of dendritic cells (DCs) in lung is critical for Th2 type immune responses in asthma and CCL20 secreted from bronchial epithelial cells (BECs) influences on the recruitment of DCs into the lung, which process is suggested to be associated with oxidative stress regulation. Clusterin, as an important oxidative stress regulatory molecule, may have a pivotal role in the pathogenesis of allergic airway inflammation in asthma.

Aim: The aim of this study was to examine if clusterin functions in regulating CCL20 production from BECs and is invovled with allergic airway inflammation through DC recruitment.

Methods: Clusterin knock-out (KO) mice were exposed to HDM extract for induction of allergic airway inflammation.The effect of clusterin on the production of CCL20 and various cytokines, development of allergic airway inflamation, immune cell recruitment into the lung, and intracellular reactive oxygen species (ROS) production was observed. CCL20 production and ROS generation was evaluated in HDM-stimulated human BECs in the setting of clusterin overexpression and downregulation.

Results: The number of total immune cells in bronchoalveolar lavage fluids (BALF) and lung were exhibited dramatic increases in clusterin KO mice. Inflammatory DCs (CD11b+CD11c+) and neutrophil populations in lung were also significantly increased, which was accompaied by enhanced CCL20 expression in BALF and oxidative stress marker expression in lung. In clusterin up- and down regulated BECs with HDM stimulation showed that secretion of CCL20 was negatively correlated with clusterin expression. Clusterin atteneuated intracellular ROS production which is related with induction of CCL20 expression after HDM stimulation.

Conclusion: Clusterin may modulate recruitment of DCs to the airway through regulating CCL20 production.