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

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...

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Autores principales:	Yanshan Jiang, Fan Li, Yanan Li, Jielin Duan, Caixia Di, Yinggang Zhu, Jingya Zhao, Xinming Jia, Jieming Qu
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	adipose tissue‐derived mesenchymal stem cells CD69 ERK1 GM‐CSF Pseudomonas aeruginosa Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/69e35340557548b1963cd89f796fad8c
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spelling	oai:doaj.org-article:69e35340557548b1963cd89f796fad8c2021-11-30T07:25:37ZCD69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection2001-132610.1002/ctm2.563https://doaj.org/article/69e35340557548b1963cd89f796fad8c2021-11-01T00:00:00Zhttps://doi.org/10.1002/ctm2.563https://doaj.org/toc/2001-1326Abstract 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.Yanshan JiangFan LiYanan LiJielin DuanCaixia DiYinggang ZhuJingya ZhaoXinming JiaJieming QuWileyarticleadipose tissue‐derived mesenchymal stem cellsCD69ERK1GM‐CSFPseudomonas aeruginosaMedicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adipose tissue‐derived mesenchymal stem cells CD69 ERK1 GM‐CSF Pseudomonas aeruginosa Medicine (General) R5-920
spellingShingle	adipose tissue‐derived mesenchymal stem cells CD69 ERK1 GM‐CSF Pseudomonas aeruginosa Medicine (General) R5-920 Yanshan Jiang Fan Li Yanan Li Jielin Duan Caixia Di Yinggang Zhu Jingya Zhao Xinming Jia Jieming Qu CD69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection
description	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.
format	article
author	Yanshan Jiang Fan Li Yanan Li Jielin Duan Caixia Di Yinggang Zhu Jingya Zhao Xinming Jia Jieming Qu
author_facet	Yanshan Jiang Fan Li Yanan Li Jielin Duan Caixia Di Yinggang Zhu Jingya Zhao Xinming Jia Jieming Qu
author_sort	Yanshan Jiang
title	CD69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection
title_short	CD69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection
title_full	CD69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection
title_fullStr	CD69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection
title_full_unstemmed	CD69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection
title_sort	cd69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against pseudomonas aeruginosa pulmonary infection
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/69e35340557548b1963cd89f796fad8c
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_version_	1718406751693307904

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

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