
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

10.1101/2024.08.27.24312640
preprint
1
Article
The post-viral GPNMB + immune niche persists in long-term Covid, asthma, and COPD
Wu Kangyun
Zhang Yong
Yin-DeClue Huiqing
Sun Kelly
Mao Dailing
Crouch Erika C.
Byers Derek E.
Holtzman Michael J.
28 8 2024
2024.08.27.24312640https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.08.27.24312640
nihpp-2024.08.27.24312640.pdf
Abstract

Epithelial injury calls for a regenerative response from a coordinated network of epithelial stem cells and immune cells. Defining this network is key to preserving the repair process for acute resolution, but also for preventing a remodeling process with chronic dysfunction. We recently identified an immune niche for basal-epithelial stem cells using mouse models of injury after respiratory viral infection. Niche function depended on an early sentinel population of monocyte-derived dendritic cells (moDCs) that provided ligand GPNMB to basal-ESC receptor CD44 for reprogramming towards chronic lung disease. These same cell and molecular control points worked directly in mouse and human basal-ESC organoids, but the findings were not yet validated in vivo in human disease. Further, persistence of GPNMB expression in moDCs and M2-macrophages in mouse models suggested utility as a long-term disease biomarker in humans. Here we show increased expression of GPNMB localized to moDC-macrophage populations in lung tissue samples from long-term Covid, asthma, and COPD. The findings thereby provide initial evidence of a persistent and correctable pathway from acute injury to chronic disease with implications for cellular reprogramming and inflammatory memory.

New and noteworthy

Recent work indicates that a sentinel immune niche provides GPNMB to epithelial stem cells to drive structural remodeling and disease as exemplified by the response to respiratory viral injury. The present study provides initial evidence that this niche can be detected in humans in the context of comparable diseases (long-term Covid, asthma, and COPD) also linked to viral infection. The results support a persistent mechanism for inflammatory disease that might be correctable with GPNMB blockade directly or indirectly through related signaling pathways.
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pmc
