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CD69 mediates the protective role of adipose tissue-derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection
- Source :
- Clinical and Translational Medicine, Clinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
- Publication Year :
- 2021
-
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.<br />1. CD69 mediates the protective effects of ASCs partly through GM‐CSF. 2. ASCs use CD69 to recognize P. aeruginosa for ERK1 activation and subsequent GM‐CSF production. 3. CD69‐ERK1 pathway plays a key role in ASCs‐based therapy against P. aeruginosa pneumonia.
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
Medicine (General)
endocrine system
Small interfering RNA
animal diseases
Cell
Medicine (miscellaneous)
chemical and pharmacologic phenomena
Biology
medicine.disease_cause
ERK1
Microbiology
Transcriptome
Mice
R5-920
Antigens, CD
medicine
Animals
Secretion
Lectins, C-Type
Pseudomonas Infections
CD69
Receptor
Research Articles
adipose tissue‐derived mesenchymal stem cells
Pseudomonas aeruginosa
GM‐CSF
Mesenchymal stem cell
hemic and immune systems
Mesenchymal Stem Cells
Pneumonia
eye diseases
Disease Models, Animal
medicine.anatomical_structure
Molecular Medicine
Research Article
Subjects
Details
- ISSN :
- 20011326
- Volume :
- 11
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Clinical and translational medicine
- Accession number :
- edsair.doi.dedup.....f7c419e10e2446af429329e886bcb166