Presentation Details
| IL-13 drives signaling pathways and chitinase expression in human and mouse olfactory stem cells Yuchen K.Sun, Binbin Ma, Haiqing Zhao, Andrew P.Lane. Johns Hopkins University, Baltimore, MD, USA |
Abstract
Background: Olfactory loss is common in chronic rhinosinusitis with nasal polyps (CRSwNP) and tracks with type‑2 (T2) inflammation. In the olfactory epithelium (OE), horizontal basal cells (HBCs) are quiescent stem cells that activate after injury. We examined HBC responses to interleukin‑13 (IL‑13) in human-relevant models. Methods: We used a mouse line with inducible, OE‑specific IL‑13 and performed single‑cell RNA‑sequencing, pathway enrichment, and immunostaining. Ex vivo, human HBCs isolated from olfactory brushings (controls, CRS, CRSwNP) were stimulated with IL‑13 and analyzed by gene expression and immunostaining. Results: In mice, IL‑13 drove HBC‑centric transcriptional programs linked to activation and immune crosstalk, including apoptosis, JAK–STAT3, and PI3K–AKT signaling. IL‑13 robustly upregulated the chitinase‑like protein Ym2 (Chi3l4) in HBCs, globose basal cells, and sustentacular cells. In human HBCs, IL‑13 increased acidic mammalian chitinase (CHIA) mRNA, with greater induction in CRS/CRSwNP donors than controls, accompanied by NOTCH1 and STAT3 upregulation. The CHIA response echoes murine Ym2, indicating a conserved chitinase‑linked pathway in HBCs under T2 conditions. Conclusions: Across mouse and human systems, IL‑13 activates signaling and chitinase programs in olfactory HBCs—Ym2 in mice and CHIA in humans—suggesting T2‑specific engagement of epithelial immune defenses by OE stem cells, potentially at the expense of sensory maintenance. These pathways nominate candidate biomarkers for CRSwNP‑related olfaction loss.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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