Tissue macrophage identity and self‐renewal
Identifieur interne : 002846 ( Istex/Corpus ); précédent : 002845; suivant : 002847Tissue macrophage identity and self‐renewal
Auteurs : Rebecca Gentek ; Kaaweh Molawi ; Michael H. SiewekeSource :
- Immunological Reviews [ 0105-2896 ] ; 2014-11.
Abstract
Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue‐resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self‐maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue‐specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue‐resident macrophages and how they differ from freshly recruited short‐lived monocyte‐derived cells. We examine whether macrophage proliferation can be qualified as self‐renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self‐renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self‐renewal could be exploited for therapeutic intervention of macrophage‐mediated pathologies by selectively targeting freshly recruited or resident macrophages.
Url:
DOI: 10.1111/imr.12224
Links to Exploration step
ISTEX:5220BE20FDF5F717974C613E4F021C8BBEB060A6Le document en format XML
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Sieweke</name><affiliation><mods:affiliation>Centre d'Immunologie de Marseille‐Luminy, Aix‐Marseille Université, UM2, Marseille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Max‐Delbrück‐Centrum für Molekulare Medizin (MDC), Robert‐Rössle‐Strasse 10, Berlin, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence to:Centre d'Immunologie de Marseille‐LuminyCampus de Luminy, Case 90613288 Marseille Cedex 9, FranceTel.: +33 4 9126 9184Fax: + 33 4 9126 9430e‐mail:</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: sieweke@ciml.univ-mrs.fr</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Immunological Reviews</title><title level="j" type="sub">Monocytes and Macrophages</title><title level="j" type="alt">IMMUNOLOGICAL REVIEWS</title><idno type="ISSN">0105-2896</idno><idno type="eISSN">1600-065X</idno><imprint><biblScope unit="vol">262</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="56">56</biblScope><biblScope unit="page" to="73">73</biblScope><biblScope unit="page-count">18</biblScope><date type="published" when="2014-11">2014-11</date></imprint><idno type="ISSN">0105-2896</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0105-2896</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue‐resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self‐maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue‐specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue‐resident macrophages and how they differ from freshly recruited short‐lived monocyte‐derived cells. We examine whether macrophage proliferation can be qualified as self‐renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self‐renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self‐renewal could be exploited for therapeutic intervention of macrophage‐mediated pathologies by selectively targeting freshly recruited or resident macrophages.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Rebecca Gentek</name><affiliations><json:string>Centre d'Immunologie de Marseille‐Luminy, Aix‐Marseille Université, UM2, Marseille, France</json:string><json:string>Institute National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France</json:string><json:string>Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France</json:string></affiliations></json:item><json:item><name>Kaaweh Molawi</name><affiliations><json:string>Centre d'Immunologie de Marseille‐Luminy, Aix‐Marseille Université, UM2, Marseille, France</json:string><json:string>Institute National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France</json:string><json:string>Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France</json:string><json:string>Max‐Delbrück‐Centrum für Molekulare Medizin (MDC), Robert‐Rössle‐Strasse 10, Berlin, Germany</json:string></affiliations></json:item><json:item><name>Michael H. Sieweke</name><affiliations><json:string>Centre d'Immunologie de Marseille‐Luminy, Aix‐Marseille Université, UM2, Marseille, France</json:string><json:string>Institute National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France</json:string><json:string>Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France</json:string><json:string>Max‐Delbrück‐Centrum für Molekulare Medizin (MDC), Robert‐Rössle‐Strasse 10, Berlin, Germany</json:string><json:string>Correspondence to:Centre d'Immunologie de Marseille‐LuminyCampus de Luminy, Case 90613288 Marseille Cedex 9, FranceTel.: +33 4 9126 9184Fax: + 33 4 9126 9430e‐mail:</json:string><json:string>E-mail: sieweke@ciml.univ-mrs.fr</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>macrophage self‐renewal</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>macrophage proliferation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>macrophage origin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>macrophage heterogeneity</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>macrophage tissue‐specific identity</value></json:item></subject><articleId><json:string>IMR12224</json:string></articleId><arkIstex>ark:/67375/WNG-9LDDN54T-R</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>reviewArticle</json:string></originalGenre><abstract>Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue‐resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self‐maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue‐specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue‐resident macrophages and how they differ from freshly recruited short‐lived monocyte‐derived cells. We examine whether macrophage proliferation can be qualified as self‐renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self‐renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self‐renewal could be exploited for therapeutic intervention of macrophage‐mediated pathologies by selectively targeting freshly recruited or resident macrophages.</abstract><qualityIndicators><score>9.232</score><pdfWordCount>12096</pdfWordCount><pdfCharCount>84410</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>18</pdfPageCount><pdfPageSize>595.276 x 782.362 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>186</abstractWordCount><abstractCharCount>1463</abstractCharCount><keywordCount>5</keywordCount></qualityIndicators><title>Tissue macrophage identity and self‐renewal</title><genre><json:string>review-article</json:string></genre><host><title>Immunological Reviews</title><language><json:string>unknown</json:string></language><doi><json:string>10.1111/(ISSN)1600-065X</json:string></doi><issn><json:string>0105-2896</json:string></issn><eissn><json:string>1600-065X</json:string></eissn><publisherId><json:string>IMR</json:string></publisherId><volume>262</volume><issue>1</issue><pages><first>56</first><last>73</last><total>18</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Invited Review</value></json:item></subject></host><ark><json:string>ark:/67375/WNG-9LDDN54T-R</json:string></ark><publicationDate>2014</publicationDate><copyrightDate>2014</copyrightDate><doi><json:string>10.1111/imr.12224</json:string></doi><id>5220BE20FDF5F717974C613E4F021C8BBEB060A6</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/5220BE20FDF5F717974C613E4F021C8BBEB060A6/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/5220BE20FDF5F717974C613E4F021C8BBEB060A6/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/5220BE20FDF5F717974C613E4F021C8BBEB060A6/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main">Tissue macrophage identity and self‐renewal</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Publishing Ltd</publisher><availability><licence>© 2014 John Wiley & Sons A/S. 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Sieweke Centre d'Immunologie de Marseille‐Luminy Campus de Luminy, Case 906 13288 Marseille Cedex 9, France Tel.: +33 4 9126 9184 Fax: + 33 4 9126 9430 e‐mail: sieweke@ciml.univ-mrs.fr</affiliation></author><idno type="istex">5220BE20FDF5F717974C613E4F021C8BBEB060A6</idno><idno type="ark">ark:/67375/WNG-9LDDN54T-R</idno><idno type="DOI">10.1111/imr.12224</idno><idno type="unit">IMR12224</idno><idno type="toTypesetVersion">file:IMR.IMR12224.pdf</idno></analytic><monogr><title level="j" type="main">Immunological Reviews</title><title level="j" type="sub">Monocytes and Macrophages</title><title level="j" type="alt">IMMUNOLOGICAL REVIEWS</title><idno type="pISSN">0105-2896</idno><idno type="eISSN">1600-065X</idno><idno type="book-DOI">10.1111/(ISSN)1600-065X</idno><idno type="book-part-DOI">10.1111/imr.2014.262.issue-1</idno><idno type="product">IMR</idno><imprint><biblScope unit="vol">262</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="56">56</biblScope><biblScope unit="page" to="73">73</biblScope><biblScope unit="page-count">18</biblScope><date type="published" when="2014-11"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract style="main" xml:id="imr12224-abs-0001"><head>Summary</head><p>Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue‐resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self‐maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue‐specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue‐resident macrophages and how they differ from freshly recruited short‐lived monocyte‐derived cells. We examine whether macrophage proliferation can be qualified as self‐renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self‐renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self‐renewal could be exploited for therapeutic intervention of macrophage‐mediated pathologies by selectively targeting freshly recruited or resident macrophages.</p></abstract><textClass><keywords><term xml:id="imr12224-kwd-0001">macrophage self‐renewal</term><term xml:id="imr12224-kwd-0002">macrophage proliferation</term><term xml:id="imr12224-kwd-0003">macrophage origin</term><term xml:id="imr12224-kwd-0004">macrophage heterogeneity</term><term xml:id="imr12224-kwd-0005">macrophage tissue‐specific identity</term></keywords><keywords rend="articleCategory"><term>Invited Review</term></keywords><keywords rend="tocHeading1"><term>Invited Reviews</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component type="serialArticle" version="2.0" xml:id="imr12224" xml:lang="en"><header><publicationMeta level="product"><doi origin="wiley" registered="yes">10.1111/(ISSN)1600-065X</doi><issn type="print">0105-2896</issn><issn type="electronic">1600-065X</issn><idGroup><id type="product" value="IMR"></id></idGroup><titleGroup><title sort="IMMUNOLOGICAL REVIEWS" type="main">Immunological Reviews</title><title type="short">Immunol Rev</title></titleGroup></publicationMeta><publicationMeta level="part" position="10"><doi origin="wiley">10.1111/imr.2014.262.issue-1</doi><titleGroup><title type="specialIssueTitle">Monocytes and Macrophages</title></titleGroup><copyright ownership="publisher">© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</copyright><numberingGroup><numbering number="262" type="journalVolume">262</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2014-11">November 2014</coverDate></publicationMeta><publicationMeta level="unit" position="50" status="forIssue" type="reviewArticle"><doi>10.1111/imr.12224</doi><idGroup><id type="unit" value="IMR12224"></id></idGroup><countGroup><count number="18" type="pageTotal"></count></countGroup><titleGroup><title type="articleCategory">Invited Review</title><title type="tocHeading1">Invited Reviews</title></titleGroup><copyright ownership="publisher">© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</copyright><eventGroup><event agent="SPS" date="2014-08-26" type="xmlCreated"></event><event type="firstOnline" date="2014-10-15"></event><event type="publishedOnlineFinalForm" date="2014-10-15"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.6.4 mode:FullText" date="2015-10-07"></event></eventGroup><numberingGroup><numbering type="pageFirst">56</numbering><numbering type="pageLast">73</numbering></numberingGroup><correspondenceTo><lineatedText><line>Correspondence to:</line><line><i>Michael H. Sieweke</i></line><line>Centre d'Immunologie de Marseille‐Luminy</line><line>Campus de Luminy, Case 906</line><line>13288 Marseille Cedex 9, France</line><line>Tel.: +33 4 9126 9184</line><line>Fax: + 33 4 9126 9430</line><line>e‐mail: <email>sieweke@ciml.univ-mrs.fr</email></line></lineatedText></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:IMR.IMR12224.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">Tissue macrophage identity and self‐renewal</title><title type="shortAuthors">Gentek et al</title></titleGroup><creators><creator affiliationRef="#imr12224-aff-0001 #imr12224-aff-0002 #imr12224-aff-0003" creatorRole="author" xml:id="imr12224-cr-0001"><personName><givenNames>Rebecca</givenNames> <familyName>Gentek</familyName></personName></creator><creator affiliationRef="#imr12224-aff-0001 #imr12224-aff-0002 #imr12224-aff-0003 #imr12224-aff-0004" creatorRole="author" xml:id="imr12224-cr-0002"><personName><givenNames>Kaaweh</givenNames> <familyName>Molawi</familyName></personName></creator><creator affiliationRef="#imr12224-aff-0001 #imr12224-aff-0002 #imr12224-aff-0003 #imr12224-aff-0004" corresponding="yes" creatorRole="author" xml:id="imr12224-cr-0003"><personName><givenNames>Michael H.</givenNames> <familyName>Sieweke</familyName></personName></creator></creators><affiliationGroup><affiliation countryCode="FR" type="organization" xml:id="imr12224-aff-0001"><orgDiv>Centre d'Immunologie de Marseille‐Luminy</orgDiv> <orgName>Aix‐Marseille Université, UM2</orgName> <address><city>Marseille</city> <country>France</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="imr12224-aff-0002"><orgDiv>Institute National de la Santé et de la Recherche Médicale (INSERM)</orgDiv> <orgName>U1104</orgName> <address><city>Marseille</city> <country>France</country></address></affiliation><affiliation countryCode="FR" type="organization" xml:id="imr12224-aff-0003"><orgDiv>Centre National de la Recherche Scientifique (CNRS)</orgDiv> <orgName>UMR7280</orgName> <address><city>Marseille</city> <country>France</country></address></affiliation><affiliation countryCode="DE" type="organization" xml:id="imr12224-aff-0004"><orgDiv>Max‐Delbrück‐Centrum für Molekulare Medizin (MDC)</orgDiv> <orgName>Robert‐Rössle‐Strasse 10</orgName> <address><city>Berlin</city> <country>Germany</country></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="imr12224-kwd-0001">macrophage self‐renewal</keyword><keyword xml:id="imr12224-kwd-0002">macrophage proliferation</keyword><keyword xml:id="imr12224-kwd-0003">macrophage origin</keyword><keyword xml:id="imr12224-kwd-0004">macrophage heterogeneity</keyword><keyword xml:id="imr12224-kwd-0005">macrophage tissue‐specific identity</keyword></keywordGroup><fundingInfo><fundingAgency>‘Agence nationale de la Recherche’</fundingAgency><fundingNumber>ANR‐11‐BSV3‐026‐01</fundingNumber></fundingInfo><fundingInfo><fundingAgency>INCA</fundingAgency><fundingNumber>PLBIO13‐244</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Fondation pour la Recherche Médicale</fundingAgency><fundingNumber>ANR‐11‐BSV3‐026‐01</fundingNumber><fundingNumber>PLBIO13‐244</fundingNumber></fundingInfo><fundingInfo><fundingAgency>HFSP</fundingAgency><fundingNumber>ANR‐11‐BSV3‐026‐01</fundingNumber><fundingNumber>PLBIO13‐244</fundingNumber><fundingNumber>20110421320</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:id="imr12224-abs-0001"><title type="main">Summary</title><p>Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue‐resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self‐maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue‐specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue‐resident macrophages and how they differ from freshly recruited short‐lived monocyte‐derived cells. We examine whether macrophage proliferation can be qualified as self‐renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self‐renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self‐renewal could be exploited for therapeutic intervention of macrophage‐mediated pathologies by selectively targeting freshly recruited or resident macrophages.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Tissue macrophage identity and self‐renewal</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Tissue macrophage identity and self‐renewal</title></titleInfo><name type="personal"><namePart type="given">Rebecca</namePart><namePart type="family">Gentek</namePart><affiliation>Centre d'Immunologie de Marseille‐Luminy, Aix‐Marseille Université, UM2, Marseille, France</affiliation><affiliation>Institute National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France</affiliation><affiliation>Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kaaweh</namePart><namePart type="family">Molawi</namePart><affiliation>Centre d'Immunologie de Marseille‐Luminy, Aix‐Marseille Université, UM2, Marseille, France</affiliation><affiliation>Institute National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France</affiliation><affiliation>Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France</affiliation><affiliation>Max‐Delbrück‐Centrum für Molekulare Medizin (MDC), Robert‐Rössle‐Strasse 10, Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael H.</namePart><namePart type="family">Sieweke</namePart><affiliation>Centre d'Immunologie de Marseille‐Luminy, Aix‐Marseille Université, UM2, Marseille, France</affiliation><affiliation>Institute National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France</affiliation><affiliation>Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France</affiliation><affiliation>Max‐Delbrück‐Centrum für Molekulare Medizin (MDC), Robert‐Rössle‐Strasse 10, Berlin, Germany</affiliation><affiliation>Correspondence to:Centre d'Immunologie de Marseille‐LuminyCampus de Luminy, Case 90613288 Marseille Cedex 9, FranceTel.: +33 4 9126 9184Fax: + 33 4 9126 9430e‐mail:</affiliation><affiliation>E-mail: sieweke@ciml.univ-mrs.fr</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="reviewArticle" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-L5L7X3NF-P">review-article</genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><dateIssued encoding="w3cdtf">2014-11</dateIssued><dateCreated encoding="w3cdtf">2014-08-26</dateCreated><copyrightDate encoding="w3cdtf">2014</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract>Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue‐resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self‐maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue‐specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue‐resident macrophages and how they differ from freshly recruited short‐lived monocyte‐derived cells. We examine whether macrophage proliferation can be qualified as self‐renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self‐renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self‐renewal could be exploited for therapeutic intervention of macrophage‐mediated pathologies by selectively targeting freshly recruited or resident macrophages.</abstract><note type="funding">‘Agence nationale de la Recherche’ - No. ANR‐11‐BSV3‐026‐01; </note><note type="funding">INCA - No. PLBIO13‐244; </note><note type="funding">Fondation pour la Recherche Médicale - No. ANR‐11‐BSV3‐026‐01; No. PLBIO13‐244; </note><note type="funding">HFSP - No. ANR‐11‐BSV3‐026‐01; No. PLBIO13‐244; No. 20110421320; </note><subject><genre>keywords</genre><topic>macrophage self‐renewal</topic><topic>macrophage proliferation</topic><topic>macrophage origin</topic><topic>macrophage heterogeneity</topic><topic>macrophage tissue‐specific identity</topic></subject><relatedItem type="host"><titleInfo><title>Immunological Reviews</title></titleInfo><titleInfo type="abbreviated"><title>Immunol Rev</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><subject><genre>article-category</genre><topic>Invited Review</topic></subject><identifier type="ISSN">0105-2896</identifier><identifier type="eISSN">1600-065X</identifier><identifier type="DOI">10.1111/(ISSN)1600-065X</identifier><identifier type="PublisherID">IMR</identifier><part><date>2014</date><detail type="title"><title>Monocytes and Macrophages</title></detail><detail type="volume"><caption>vol.</caption><number>262</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>56</start><end>73</end><total>18</total></extent></part></relatedItem><identifier type="istex">5220BE20FDF5F717974C613E4F021C8BBEB060A6</identifier><identifier type="ark">ark:/67375/WNG-9LDDN54T-R</identifier><identifier type="DOI">10.1111/imr.12224</identifier><identifier type="ArticleID">IMR12224</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2014 John Wiley & Sons A/S. 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