Mesenchymal stem cell exosomal tsRNA-21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization
•Mesenchymal stem cells derived exosomes suppressed M1-type polarization macrophages.•Small RNA-Seq identified tsRNA-21109 up-regulated in macrophage to response MSC-Exo.•Inhibiting tsRNA-21109 expression promote M1-type polarization macrophages.•tsRNA-21109 expression was associated with clinical S...
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Veröffentlicht in: | Molecular immunology 2021-11, Vol.139, p.106-114 |
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description | •Mesenchymal stem cells derived exosomes suppressed M1-type polarization macrophages.•Small RNA-Seq identified tsRNA-21109 up-regulated in macrophage to response MSC-Exo.•Inhibiting tsRNA-21109 expression promote M1-type polarization macrophages.•tsRNA-21109 expression was associated with clinical SLE patient data.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with M1-type macrophage activation. Mesenchymal stem cells (MSCs) therapies have shown promise in models of pathologies relevant to SLE, while the function and mechanism of MSC-derived exosomes (MSC-exo) were still unclear. We aimed to interrogate the effect of MSC-exo on M1-type polarization of macrophage and investigate mechanisms underlying MSC-exo. Exosomes were isolated from MSC and the effect of MSC-exo on macrophage polarization was evaluated. The key tRNA-derived fragments (tRFs) carried by exosomes were identified by small RNA sequencing and verified in clinical samples. The effect of exosomal-tRFs on macrophage polarization was examined. In this study, MSC-exo dramatically suppressed expression of M1 markers, and reduced the levels of TNF-α and IL-1β, while increased M2 markers in macrophages. A total of 243 differently expressed tRFs (DEtRFs) were identified between MSC-exo treated and untreated macrophage, among which 103 DEtRFs were up-regulated in response to MSC-exo treatment, including tsRNA-21109. The target genes of tsRNA-21109 were mainly enriched in DNA transcription-related GO function, and mainly involved in inflammatory-related pathways, including Rap1, Ras, Hippo, Wnt, MAPK, TGF-beta signaling pathway. The tsRNA-21109 was lowly expressed in clinical samples and was associated with the patient data in SLE. Compared to the normal MSC-exo, the tsRNA-21109-privative MSC-exo up-regulated M1 marker (CD80, NOS2, MCP1) and down-regulated M2 marker (CD206, ARG1, MRC2), also increased the levels of TNF-α and IL-1β in macrophages. Western blot and immunofluorescence confirmed that the proportion of CD80/ARG-1 was increased in macrophages treated with tsRNA-21109-privatived MSC-exo compared to that with control MSC-exo. In conclusion, MSC-exo inhibited the M1-type polarization of macrophages, possibly through transferring tsRNA-21109, which may develop as a novel therapeutic target for SLE. |
doi_str_mv | 10.1016/j.molimm.2021.08.015 |
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with M1-type macrophage activation. Mesenchymal stem cells (MSCs) therapies have shown promise in models of pathologies relevant to SLE, while the function and mechanism of MSC-derived exosomes (MSC-exo) were still unclear. We aimed to interrogate the effect of MSC-exo on M1-type polarization of macrophage and investigate mechanisms underlying MSC-exo. Exosomes were isolated from MSC and the effect of MSC-exo on macrophage polarization was evaluated. The key tRNA-derived fragments (tRFs) carried by exosomes were identified by small RNA sequencing and verified in clinical samples. The effect of exosomal-tRFs on macrophage polarization was examined. In this study, MSC-exo dramatically suppressed expression of M1 markers, and reduced the levels of TNF-α and IL-1β, while increased M2 markers in macrophages. A total of 243 differently expressed tRFs (DEtRFs) were identified between MSC-exo treated and untreated macrophage, among which 103 DEtRFs were up-regulated in response to MSC-exo treatment, including tsRNA-21109. The target genes of tsRNA-21109 were mainly enriched in DNA transcription-related GO function, and mainly involved in inflammatory-related pathways, including Rap1, Ras, Hippo, Wnt, MAPK, TGF-beta signaling pathway. The tsRNA-21109 was lowly expressed in clinical samples and was associated with the patient data in SLE. Compared to the normal MSC-exo, the tsRNA-21109-privative MSC-exo up-regulated M1 marker (CD80, NOS2, MCP1) and down-regulated M2 marker (CD206, ARG1, MRC2), also increased the levels of TNF-α and IL-1β in macrophages. Western blot and immunofluorescence confirmed that the proportion of CD80/ARG-1 was increased in macrophages treated with tsRNA-21109-privatived MSC-exo compared to that with control MSC-exo. In conclusion, MSC-exo inhibited the M1-type polarization of macrophages, possibly through transferring tsRNA-21109, which may develop as a novel therapeutic target for SLE.</description><identifier>ISSN: 0161-5890</identifier><identifier>EISSN: 1872-9142</identifier><identifier>DOI: 10.1016/j.molimm.2021.08.015</identifier><language>eng</language><publisher>Elsevier Ltd</publisher><subject>Exosome ; Macrophage polarization ; Mesenchymal stem cell ; Systemic lupus erythematosus ; tRNA-derived fragments (tRFs)</subject><ispartof>Molecular immunology, 2021-11, Vol.139, p.106-114</ispartof><rights>2021 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c339t-f2f30b6489d3085b691c247e77bcba33beab4eeed61474b198de161c1afb52043</citedby><cites>FETCH-LOGICAL-c339t-f2f30b6489d3085b691c247e77bcba33beab4eeed61474b198de161c1afb52043</cites><orcidid>0000-0001-7891-8514 ; 0000-0002-0596-6715</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.molimm.2021.08.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids></links><search><creatorcontrib>Dou, Rui</creatorcontrib><creatorcontrib>Zhang, Xiulei</creatorcontrib><creatorcontrib>Xu, Xiangdong</creatorcontrib><creatorcontrib>Wang, Pei</creatorcontrib><creatorcontrib>Yan, Beizhan</creatorcontrib><title>Mesenchymal stem cell exosomal tsRNA-21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization</title><title>Molecular immunology</title><description>•Mesenchymal stem cells derived exosomes suppressed M1-type polarization macrophages.•Small RNA-Seq identified tsRNA-21109 up-regulated in macrophage to response MSC-Exo.•Inhibiting tsRNA-21109 expression promote M1-type polarization macrophages.•tsRNA-21109 expression was associated with clinical SLE patient data.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with M1-type macrophage activation. Mesenchymal stem cells (MSCs) therapies have shown promise in models of pathologies relevant to SLE, while the function and mechanism of MSC-derived exosomes (MSC-exo) were still unclear. We aimed to interrogate the effect of MSC-exo on M1-type polarization of macrophage and investigate mechanisms underlying MSC-exo. Exosomes were isolated from MSC and the effect of MSC-exo on macrophage polarization was evaluated. The key tRNA-derived fragments (tRFs) carried by exosomes were identified by small RNA sequencing and verified in clinical samples. The effect of exosomal-tRFs on macrophage polarization was examined. In this study, MSC-exo dramatically suppressed expression of M1 markers, and reduced the levels of TNF-α and IL-1β, while increased M2 markers in macrophages. A total of 243 differently expressed tRFs (DEtRFs) were identified between MSC-exo treated and untreated macrophage, among which 103 DEtRFs were up-regulated in response to MSC-exo treatment, including tsRNA-21109. The target genes of tsRNA-21109 were mainly enriched in DNA transcription-related GO function, and mainly involved in inflammatory-related pathways, including Rap1, Ras, Hippo, Wnt, MAPK, TGF-beta signaling pathway. The tsRNA-21109 was lowly expressed in clinical samples and was associated with the patient data in SLE. Compared to the normal MSC-exo, the tsRNA-21109-privative MSC-exo up-regulated M1 marker (CD80, NOS2, MCP1) and down-regulated M2 marker (CD206, ARG1, MRC2), also increased the levels of TNF-α and IL-1β in macrophages. Western blot and immunofluorescence confirmed that the proportion of CD80/ARG-1 was increased in macrophages treated with tsRNA-21109-privatived MSC-exo compared to that with control MSC-exo. In conclusion, MSC-exo inhibited the M1-type polarization of macrophages, possibly through transferring tsRNA-21109, which may develop as a novel therapeutic target for SLE.</description><subject>Exosome</subject><subject>Macrophage polarization</subject><subject>Mesenchymal stem cell</subject><subject>Systemic lupus erythematosus</subject><subject>tRNA-derived fragments (tRFs)</subject><issn>0161-5890</issn><issn>1872-9142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE9v1DAQxS1UJLYL34CDj1wSPI7z74JUVW1BakFCcLZsZ9L1yo5T21uRfnoStmdOoxm99zTvR8hHYCUwaD4fSx-c9b7kjEPJupJB_YbsoGt50YPgF2S3yqCou569I5cpHRljDWvqHXl5wISTOSxeOZoyemrQOYp_QgrbKaef368KDsB6qpzDZ6sy0rRsUmuoO82nRDEu-YBe5ZDWTS_UTgerbbbTI_XKxDAf1CPSB6BzcCraF5VtmN6Tt6NyCT-8zj35fXvz6_prcf_j7tv11X1hqqrPxcjHiulGdP1Qsa7WTQ-GixbbVhutqkqj0gIRhwZEKzT03YBrWQNq1DVnotqTT-fcOYanE6YsvU1bSzVhOCXJ66bjoq-hXqXiLF1_TiniKOdovYqLBCY31PIoz6jlhlqyTrJ_ti9nG641ni1GmYxdqeJgI5osh2D_H_AX0GyL0w</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Dou, Rui</creator><creator>Zhang, Xiulei</creator><creator>Xu, Xiangdong</creator><creator>Wang, Pei</creator><creator>Yan, Beizhan</creator><general>Elsevier Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7891-8514</orcidid><orcidid>https://orcid.org/0000-0002-0596-6715</orcidid></search><sort><creationdate>202111</creationdate><title>Mesenchymal stem cell exosomal tsRNA-21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization</title><author>Dou, Rui ; Zhang, Xiulei ; Xu, Xiangdong ; Wang, Pei ; Yan, Beizhan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-f2f30b6489d3085b691c247e77bcba33beab4eeed61474b198de161c1afb52043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Exosome</topic><topic>Macrophage polarization</topic><topic>Mesenchymal stem cell</topic><topic>Systemic lupus erythematosus</topic><topic>tRNA-derived fragments (tRFs)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dou, Rui</creatorcontrib><creatorcontrib>Zhang, Xiulei</creatorcontrib><creatorcontrib>Xu, Xiangdong</creatorcontrib><creatorcontrib>Wang, Pei</creatorcontrib><creatorcontrib>Yan, Beizhan</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dou, Rui</au><au>Zhang, Xiulei</au><au>Xu, Xiangdong</au><au>Wang, Pei</au><au>Yan, Beizhan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenchymal stem cell exosomal tsRNA-21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization</atitle><jtitle>Molecular immunology</jtitle><date>2021-11</date><risdate>2021</risdate><volume>139</volume><spage>106</spage><epage>114</epage><pages>106-114</pages><issn>0161-5890</issn><eissn>1872-9142</eissn><abstract>•Mesenchymal stem cells derived exosomes suppressed M1-type polarization macrophages.•Small RNA-Seq identified tsRNA-21109 up-regulated in macrophage to response MSC-Exo.•Inhibiting tsRNA-21109 expression promote M1-type polarization macrophages.•tsRNA-21109 expression was associated with clinical SLE patient data.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with M1-type macrophage activation. Mesenchymal stem cells (MSCs) therapies have shown promise in models of pathologies relevant to SLE, while the function and mechanism of MSC-derived exosomes (MSC-exo) were still unclear. We aimed to interrogate the effect of MSC-exo on M1-type polarization of macrophage and investigate mechanisms underlying MSC-exo. Exosomes were isolated from MSC and the effect of MSC-exo on macrophage polarization was evaluated. The key tRNA-derived fragments (tRFs) carried by exosomes were identified by small RNA sequencing and verified in clinical samples. The effect of exosomal-tRFs on macrophage polarization was examined. In this study, MSC-exo dramatically suppressed expression of M1 markers, and reduced the levels of TNF-α and IL-1β, while increased M2 markers in macrophages. A total of 243 differently expressed tRFs (DEtRFs) were identified between MSC-exo treated and untreated macrophage, among which 103 DEtRFs were up-regulated in response to MSC-exo treatment, including tsRNA-21109. The target genes of tsRNA-21109 were mainly enriched in DNA transcription-related GO function, and mainly involved in inflammatory-related pathways, including Rap1, Ras, Hippo, Wnt, MAPK, TGF-beta signaling pathway. The tsRNA-21109 was lowly expressed in clinical samples and was associated with the patient data in SLE. Compared to the normal MSC-exo, the tsRNA-21109-privative MSC-exo up-regulated M1 marker (CD80, NOS2, MCP1) and down-regulated M2 marker (CD206, ARG1, MRC2), also increased the levels of TNF-α and IL-1β in macrophages. Western blot and immunofluorescence confirmed that the proportion of CD80/ARG-1 was increased in macrophages treated with tsRNA-21109-privatived MSC-exo compared to that with control MSC-exo. In conclusion, MSC-exo inhibited the M1-type polarization of macrophages, possibly through transferring tsRNA-21109, which may develop as a novel therapeutic target for SLE.</abstract><pub>Elsevier Ltd</pub><doi>10.1016/j.molimm.2021.08.015</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-7891-8514</orcidid><orcidid>https://orcid.org/0000-0002-0596-6715</orcidid></addata></record> |
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subjects | Exosome Macrophage polarization Mesenchymal stem cell Systemic lupus erythematosus tRNA-derived fragments (tRFs) |
title | Mesenchymal stem cell exosomal tsRNA-21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization |
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