Journal of Clinical and Cellular Immunology
Open Access

Chitinase 3-like-1 and its receptors in Hermansky-Pudlak syndrome-associated lung disease

4^th International Conference and Exhibition on Immunology

September 28-30, 2015 Crowne Plaza Houston River Oaks, Houston, TX, USA

Yang Zhou1,2, Chuan Hua He1,2, Erica L Herzog2, Xueyan Peng2, Chang-Min Lee1,2, Tung H Nguyen1, Mridu Gulati2, Bernadette R Gochuico3, William A Gahl3, Martin L Slade2, Chun Geun Lee1,2 and Jack A Elias1,2

1Brown University, USA 2Yale University, USA 3National Institute of Health, USA

Posters-Accepted Abstracts: J Clin Cell Immunol

Abstract :

Hermansky-Pudlak Syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in BLOC-3 mutant HPS-1 and HPS-4 patients. Chitinase 3-like-1 (CHI3L1), a prototypic chitinase-like protein, plays a protective role by ameliorating cell death and stimulating fibro-proliferative repair. Here we demonstrate that circulating CHI3L1 levels are higher in HPS patients with pulmonary fibrosis compared to those that remain fibrosis-free and that these levels associate with disease severity. Using murine models we also demonstrate that a defect in CHI3L1 inhibition of epithelial apoptosis and exaggerated CHI3L1-driven fibro-proliferation play important roles in HPS fibrosis. Lastly we demonstrate that these divergent responses are mediated by differences in the trafficking and effector functions of two CHI3L1 receptors. Specifically, the enhanced sensitivity to apoptosis is due to the BLOC-3 dependent and thus abnormal, trafficking of IL-13Ra2. In contrast, the fibrosis is due to interactions of CHI3L1 and CRTH2, which traffics normally in BLOC-3 HPS.

Biography :

Email: Yang_Zhou@brown.edu