CD69 mediates the protective role of adipose tissue-derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection

  • Clin Transl Med. 2021 Nov;11(11):e563. doi: 10.1002/ctm2.563.
Yanshan Jiang  1  2  3  4 ,  Fan Li  4 ,  Yanan Li  1  2  3  4 ,  Jielin Duan  4 ,  Caixia Di  1  2  3 ,  Yinggang Zhu  5 ,  Jingya Zhao  1  2  3 ,  Xinming Jia  4 ,  Jieming Qu  1  2  3
Affiliations
  • 1. Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 2. Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
  • 3. Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, 200025, China.
  • 4. Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • 5. Department of Pulmonary and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, China.
PMID: 34841721 DOI: 10.1002/ctm2.563
Abstract

Background: Our previous study shows that Adipose tissue-derived mesenchymal stem cells (ASCs) are a promising strategy for cell-based therapy against pulmonary Infection with Pseudomonas aeruginosa (P. aeruginosa), but the underlying mechanisms remain unclear.

Methods: cDNA microarray assay was performed to explore the transcriptome of ASCs primed by P. aeruginosa. Small interfering RNA (siRNA) was constructed to select the receptor candidates for P. aeruginosa recognition and granulocyte-macrophage colony-stimulating factor (GM-CSF) production in ASCs. The soluble protein chimeras containing the extracellular domain of human CD69 fused to the Fc region of human immunoglobulin IgG1 were used as a probe to validate the recognition of P. aeruginosa. The association between CD69 and extracellular regulated protein kinases 1/2 (ERK1/2) was explored via co-immunoprecipitation, siRNA, and inhibitor. The murine models of P. aeruginosa pneumonia treated with WT-ASCs, GM-CSF-/- -ASCs CD69-/- -ASCs or ERK1-/- -ASCs were used to determine the role of GM-CSF, CD69, and ERK1 in ASCs against P. aeruginosa Infection.

Results: We showed that C-type lectin receptor CD69 mediated the protective effects of ASCs partly through GM-CSF. CD69 could specifically recognize P. aeruginosa and regulate GM-CSF secretion of ASCs. CD69 regulated the production of GM-CSF via ERK1 in ASCs after P. aeruginosa Infection. Moreover, the Administration of ASCs with deficiency of CD69 or ERK1 completely blocked its protective effects in a murine model of P. aeruginosa pneumonia.

Conclusions: CD69 recognizes P. aeruginosa and further facilitates ERK1 activation, which plays a crucial role in ASCs-based therapy against P. aeruginosa pneumonia. CD69 may be a novel target molecule to improve ASCs-based therapy against P. aeruginosa Infection.

Keywords
CD69; ERK1; GM-CSF; Pseudomonas aeruginosa; adipose tissue-derived mesenchymal stem cells.