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CXCR3-independent role of CXCL10 in alveolar epithelial repair.

Authors :
Zhang Y
Liang J
Ye J
Liu N
Noble PW
Jiang D
Source :
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2024 Aug 01; Vol. 327 (2), pp. L160-L172. Date of Electronic Publication: 2024 May 21.
Publication Year :
2024

Abstract

The alveolar type II epithelial cells (AEC2s) act as stem cells in the lung for alveolar epithelial maintenance and repair. Chemokine C-X-C motif chemokine 10 (CXCL10) is expressed in injured tissues, modulating multiple cellular functions. AEC2s, previously reported to release chemokines to recruit leukocytes, were found in our study to secrete CXCL10 after bleomycin injury. We found that Sftpc-Cxcl10 transgenic mice were protected from bleomycin injury. The transgenic mice showed an increase in the AEC2 population in the lung by flow cytometry analysis. Both endogenous and exogenous CXCL10 promoted the colony formation efficiency of AEC2s in a three-dimensional (3-D) organoid growth assay. We identified that the regenerative effect of CXCL10 was CXCR3 independent using Cxcr3 -deficient mice, but it was related to the TrkA pathway. Binding experiments showed that CXCL10 interacted with TrkA directly and reversibly. This study demonstrates a previously unidentified AEC2 autocrine signaling of CXCL10 to promote their regeneration and proliferation, probably involving a CXCR3-independent TrkA pathway. NEW & NOTEWORTHY CXCL10 may aid in lung injury recovery by promoting the proliferation of alveolar stem cells and using a distinct regulatory pathway from the classical one.

Details

Language :
English
ISSN :
1522-1504
Volume :
327
Issue :
2
Database :
MEDLINE
Journal :
American journal of physiology. Lung cellular and molecular physiology
Publication Type :
Academic Journal
Accession number :
38771132
Full Text :
https://doi.org/10.1152/ajplung.00301.2023