ASCs Activate cGAS-Type I IFNs-IL-7 Axis Via Pseudomonas aeruginosa-Derived Outer Membrane Vesicles to Resolve Pneumonia

Abstract Mesenchymal stem cells (MSCs) therapy could efficiently attenuate LPS-induced acute lung injury and Pseudomonas aeruginosa (PA)-induced acute pneumonia. However, the underlying molecular mechanisms are still elusive. Here, we report that PA-derived outer membrane vesicles (OMVs) trigger mou...

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Veröffentlicht in:	Stem cells (Dayton, Ohio) Ohio), 2023-05, Vol.41 (5), p.468-481
Hauptverfasser:	Di, Caixia, Jiang, Yanshan, Li, Lulu, Shi, Mengmeng, Zhu, Yinggang, Zhang, Jing, Song, Yuanlin, Su, Xiao, Qu, Jieming
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals DNA - metabolism Interferon Type I - metabolism Interleukin-7 Membrane Proteins - genetics Mice Nucleotidyltransferases - genetics Nucleotidyltransferases - metabolism Pneumonia - therapy Pseudomonas aeruginosa - genetics Pseudomonas aeruginosa - metabolism
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container_title	Stem cells (Dayton, Ohio)
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creator	Di, Caixia Jiang, Yanshan Li, Lulu Shi, Mengmeng Zhu, Yinggang Zhang, Jing Song, Yuanlin Su, Xiao Qu, Jieming
description	Abstract Mesenchymal stem cells (MSCs) therapy could efficiently attenuate LPS-induced acute lung injury and Pseudomonas aeruginosa (PA)-induced acute pneumonia. However, the underlying molecular mechanisms are still elusive. Here, we report that PA-derived outer membrane vesicles (OMVs) trigger mouse primary adipose tissue-derived mesenchymal stem cells (ASCs) to upregulate cyclic GMP-AMP synthase (cGAS) for sensing of double-stranded DNA (dsDNA) and the expression of interleukin (IL)-7. Loss of cGAS-interferon (IFN)-β axis abolished the protective function of ASCs to PA-induced acute pneumonia in mice. Mechanistically, OMVs-delivered PA dsDNA primes cGAS-stimulator of interferon genes (STING) signaling pathway and increases the IL-7 production in ASCs via IFN-β signaling. Meanwhile, dsDNA-primed ASCs furthermore amplifies IL-7 expression in primary lung epithelial cells and mouse lung epithelial (MLE)-12 cell line via increased IFN-β. Our findings thus implicate a molecular mechanism that ASCs recognize PA-OMVs-derived dsDNA to secrete IL-7 via activating cGAS, suggesting a potential therapeutic strategy of ASCs transfer for PA-induced lung infection and inflammation. Graphical Abstract Graphical Abstract ASCs activate cGAS-type I IFNs-IL-7 axis via Pseudomonas aeruginosa-derived outer membrane vesicles to resolve pneumonia.
doi_str_mv	10.1093/stmcls/sxad016
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However, the underlying molecular mechanisms are still elusive. Here, we report that PA-derived outer membrane vesicles (OMVs) trigger mouse primary adipose tissue-derived mesenchymal stem cells (ASCs) to upregulate cyclic GMP-AMP synthase (cGAS) for sensing of double-stranded DNA (dsDNA) and the expression of interleukin (IL)-7. Loss of cGAS-interferon (IFN)-β axis abolished the protective function of ASCs to PA-induced acute pneumonia in mice. Mechanistically, OMVs-delivered PA dsDNA primes cGAS-stimulator of interferon genes (STING) signaling pathway and increases the IL-7 production in ASCs via IFN-β signaling. Meanwhile, dsDNA-primed ASCs furthermore amplifies IL-7 expression in primary lung epithelial cells and mouse lung epithelial (MLE)-12 cell line via increased IFN-β. Our findings thus implicate a molecular mechanism that ASCs recognize PA-OMVs-derived dsDNA to secrete IL-7 via activating cGAS, suggesting a potential therapeutic strategy of ASCs transfer for PA-induced lung infection and inflammation. Graphical Abstract Graphical Abstract ASCs activate cGAS-type I IFNs-IL-7 axis via Pseudomonas aeruginosa-derived outer membrane vesicles to resolve pneumonia.</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1093/stmcls/sxad016</identifier><identifier>PMID: 36827175</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Animals ; DNA - metabolism ; Interferon Type I - metabolism ; Interleukin-7 ; Membrane Proteins - genetics ; Mice ; Nucleotidyltransferases - genetics ; Nucleotidyltransferases - metabolism ; Pneumonia - therapy ; Pseudomonas aeruginosa - genetics ; Pseudomonas aeruginosa - metabolism</subject><ispartof>Stem cells (Dayton, Ohio), 2023-05, Vol.41 (5), p.468-481</ispartof><rights>The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2023</rights><rights>The Author(s) 2023. 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However, the underlying molecular mechanisms are still elusive. Here, we report that PA-derived outer membrane vesicles (OMVs) trigger mouse primary adipose tissue-derived mesenchymal stem cells (ASCs) to upregulate cyclic GMP-AMP synthase (cGAS) for sensing of double-stranded DNA (dsDNA) and the expression of interleukin (IL)-7. Loss of cGAS-interferon (IFN)-β axis abolished the protective function of ASCs to PA-induced acute pneumonia in mice. Mechanistically, OMVs-delivered PA dsDNA primes cGAS-stimulator of interferon genes (STING) signaling pathway and increases the IL-7 production in ASCs via IFN-β signaling. Meanwhile, dsDNA-primed ASCs furthermore amplifies IL-7 expression in primary lung epithelial cells and mouse lung epithelial (MLE)-12 cell line via increased IFN-β. Our findings thus implicate a molecular mechanism that ASCs recognize PA-OMVs-derived dsDNA to secrete IL-7 via activating cGAS, suggesting a potential therapeutic strategy of ASCs transfer for PA-induced lung infection and inflammation. Graphical Abstract Graphical Abstract ASCs activate cGAS-type I IFNs-IL-7 axis via Pseudomonas aeruginosa-derived outer membrane vesicles to resolve pneumonia.</description><subject>Animals</subject><subject>DNA - metabolism</subject><subject>Interferon Type I - metabolism</subject><subject>Interleukin-7</subject><subject>Membrane Proteins - genetics</subject><subject>Mice</subject><subject>Nucleotidyltransferases - genetics</subject><subject>Nucleotidyltransferases - metabolism</subject><subject>Pneumonia - therapy</subject><subject>Pseudomonas aeruginosa - genetics</subject><subject>Pseudomonas aeruginosa - metabolism</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v2zAMhoWhw9KPXXcsdOwOaqXIlq2jka1tgHQtmixXg5bpQYMdZaIdpP9-LpL22gtJgA9fEA9j35S8VtLqG-o719IN7aGWynxipypNrEisyk_GWRojUmnthJ0R_ZVSJWmef2ETbfJpprL0lO2L5Yx44Xq_gx65uyuWYvWyRT7n89tfJOYLkfFi74mvPfAnwqEOXdgAccA4_PGbQCB-YPQ7rPnj0GPkD9hVETbI10jetUi8D_wZKbQ75E8bHMZ7DxfscwMt4ddjP2e_b3-uZvdi8Xg3nxUL4fTU9qKuEJSrtFKZa1BnkNkswTqHpErGklc6ryqppERAaGrTjHtjwDgNmKJO9Tm7OuRuY_g3IPVl58lh244fhoHKaZZLaWxq5YheH1AXA1HEptxG30F8KZUsX22XB9vl0fZ4cHnMHqoO63f8Te8IfD8AYdh-FPYflVSMsA</recordid><startdate>20230515</startdate><enddate>20230515</enddate><creator>Di, Caixia</creator><creator>Jiang, Yanshan</creator><creator>Li, Lulu</creator><creator>Shi, Mengmeng</creator><creator>Zhu, Yinggang</creator><creator>Zhang, Jing</creator><creator>Song, Yuanlin</creator><creator>Su, Xiao</creator><creator>Qu, Jieming</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0464-544X</orcidid><orcidid>https://orcid.org/0000-0002-8692-8365</orcidid></search><sort><creationdate>20230515</creationdate><title>ASCs Activate cGAS-Type I IFNs-IL-7 Axis Via Pseudomonas aeruginosa-Derived Outer Membrane Vesicles to Resolve Pneumonia</title><author>Di, Caixia ; Jiang, Yanshan ; Li, Lulu ; Shi, Mengmeng ; Zhu, Yinggang ; Zhang, Jing ; Song, Yuanlin ; Su, Xiao ; Qu, Jieming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c329t-dbea1cb3117cfe37a7974ed8a4b48a48b38bb0100eaeafd6f79766a6c3ae5e353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>DNA - metabolism</topic><topic>Interferon Type I - metabolism</topic><topic>Interleukin-7</topic><topic>Membrane Proteins - genetics</topic><topic>Mice</topic><topic>Nucleotidyltransferases - genetics</topic><topic>Nucleotidyltransferases - metabolism</topic><topic>Pneumonia - therapy</topic><topic>Pseudomonas aeruginosa - genetics</topic><topic>Pseudomonas aeruginosa - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di, Caixia</creatorcontrib><creatorcontrib>Jiang, Yanshan</creatorcontrib><creatorcontrib>Li, Lulu</creatorcontrib><creatorcontrib>Shi, Mengmeng</creatorcontrib><creatorcontrib>Zhu, Yinggang</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Song, Yuanlin</creatorcontrib><creatorcontrib>Su, Xiao</creatorcontrib><creatorcontrib>Qu, Jieming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di, Caixia</au><au>Jiang, Yanshan</au><au>Li, Lulu</au><au>Shi, Mengmeng</au><au>Zhu, Yinggang</au><au>Zhang, Jing</au><au>Song, Yuanlin</au><au>Su, Xiao</au><au>Qu, Jieming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ASCs Activate cGAS-Type I IFNs-IL-7 Axis Via Pseudomonas aeruginosa-Derived Outer Membrane Vesicles to Resolve Pneumonia</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2023-05-15</date><risdate>2023</risdate><volume>41</volume><issue>5</issue><spage>468</spage><epage>481</epage><pages>468-481</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>Abstract Mesenchymal stem cells (MSCs) therapy could efficiently attenuate LPS-induced acute lung injury and Pseudomonas aeruginosa (PA)-induced acute pneumonia. 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Our findings thus implicate a molecular mechanism that ASCs recognize PA-OMVs-derived dsDNA to secrete IL-7 via activating cGAS, suggesting a potential therapeutic strategy of ASCs transfer for PA-induced lung infection and inflammation. Graphical Abstract Graphical Abstract ASCs activate cGAS-type I IFNs-IL-7 axis via Pseudomonas aeruginosa-derived outer membrane vesicles to resolve pneumonia.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>36827175</pmid><doi>10.1093/stmcls/sxad016</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-0464-544X</orcidid><orcidid>https://orcid.org/0000-0002-8692-8365</orcidid></addata></record>
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subjects	Animals DNA - metabolism Interferon Type I - metabolism Interleukin-7 Membrane Proteins - genetics Mice Nucleotidyltransferases - genetics Nucleotidyltransferases - metabolism Pneumonia - therapy Pseudomonas aeruginosa - genetics Pseudomonas aeruginosa - metabolism
title	ASCs Activate cGAS-Type I IFNs-IL-7 Axis Via Pseudomonas aeruginosa-Derived Outer Membrane Vesicles to Resolve Pneumonia
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