2. Academic Validation
  3. CXCR3-Independent Role of CXCL10 in Alveolar Epithelial Repair

CXCR3-Independent Role of CXCL10 in Alveolar Epithelial Repair

  • Am J Physiol Lung Cell Mol Physiol. 2024 May 21. doi: 10.1152/ajplung.00301.2023.
Yanli Zhang 1,  Jiurong Liang 2,  Jun Ye 1,  Ningshan Liu 3,  Paul W Noble 2,  Dianhua Jiang 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 2 Cedars-Sinai Medical Center, Los Angeles, CA, United States.
  • 3 Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, China.
PMID: 38771132 DOI: 10.1152/ajplung.00301.2023
Abstract

The alveolar Type II epithelial (AEC2) cells act as stem cells in the lung for alveolar epithelial maintenance and repair. Chemokine 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 3D 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.

Keywords

Alveolar Repair; CXCL10; TrkA; alveolar Type II epithelial cells.

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