Chitinase 3-Like-1/BRP-39 regulates extracellular matrix remodeling during allergic fungal asthma

---

Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B872
Abstract ID: 5999

Presenting Author:
Diandra Ellis , Doctoral Candidate at Tulane Univ. Sch. of Med.

Abstract:

We previously reported that fungal-sensitized human asthmatics had higher levels of the chitinase-like protein YKL-40 in sputum than non-fungal sensitized asthmatics. Unexpectedly, we found that mice deficient in BRP-39 (Chi3l1-/- mice; the murine ortholog of human YKL-40) had increased airway hyperreactivity (AHR) during experimental allergic fungal asthma, despite no correlation with classic drivers of AHR (type 2 and eosinophilic responses). BRP-39 has been reported to bind lectins and complex carbohydrates and is involved in non-immune processes such as cell proliferation, angiogenesis and tissue remodeling. The extracellular matrix (ECM) of the lung is mainly comprised of collagen and elastin that provides elasticity and resilience to compressive and expanding forces. We found that Chi3l1-/- mice subjected to allergic fungal asthma demonstrated restrictions in lung mechanics due to increased elastic stiffness in the conducting airways and the alveolar/parenchymal compartment. This correlated with increased levels of collagen and elastin in mutant mice. ECM enzymes involved in matrix remodeling of collagen and elastin, such as matrix metalloproteinases (MMPs) 2, 3, 9, and 12, were reduced in mutant mice. We further identified BRP-39 dependent differences in MMP secretion by stimulating primary lung fibroblasts. Ultimately, these findings highlight BRP-39 as a crucial regulator of MMPs needed to turnover lung ECM proteins during the progression of allergic fungal asthma.