Wnt5a is a TLR2/4-ligand that induces tolerance in human myeloid cells
Identifieur interne : 000273 ( Main/Exploration ); précédent : 000272; suivant : 000274Wnt5a is a TLR2/4-ligand that induces tolerance in human myeloid cells
Auteurs : Meliha Mehmeti [Suède] ; Caroline Bergenfelz [Suède] ; Eva K Llberg [Suède] ; Camilla Rydberg Millrud [Suède] ; Per Björk [Suède] ; Fredrik Ivars [Suède] ; Bengt Johansson-Lindbom [Suède] ; Sven Kjellström [Suède] ; Ingemar André [Suède] ; Karin Leandersson [Suède]Source :
- Communications Biology [ 2399-3642 ] ; 2019.
Abstract
Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and
Url:
DOI: 10.1038/s42003-019-0432-4
PubMed: 31098409
PubMed Central: 6509336
Affiliations:
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last="Ivars">Fredrik Ivars</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0930 2361</institution-id><institution-id institution-id-type="GRID">grid.4514.4</institution-id><institution>Immunology Unit, Department of Experimental Medicine,</institution><institution>Lund University,</institution></institution-wrap>Lund, 22184 Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Lund</wicri:regionArea></affiliation></author><author><name sortKey="Johansson Lindbom, Bengt" sort="Johansson Lindbom, Bengt" uniqKey="Johansson Lindbom B" first="Bengt" last="Johansson-Lindbom">Bengt Johansson-Lindbom</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0930 2361</institution-id><institution-id institution-id-type="GRID">grid.4514.4</institution-id><institution>Immunology Unit, Department of Experimental 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wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0930 2361</institution-id><institution-id institution-id-type="GRID">grid.4514.4</institution-id><institution>Center for Molecular Protein Science,</institution><institution>Lund University,</institution></institution-wrap>Lund, 22362 Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Lund</wicri:regionArea></affiliation></author><author><name sortKey="Leandersson, Karin" sort="Leandersson, Karin" uniqKey="Leandersson K" first="Karin" last="Leandersson">Karin Leandersson</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0930 2361</institution-id><institution-id institution-id-type="GRID">grid.4514.4</institution-id><institution>Cancer Immunology, Department of Translational Medicine,</institution><institution>Lund University,</institution></institution-wrap>Malmö, 21428 Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Malmö</wicri:regionArea></affiliation></author></analytic><series><title level="j">Communications Biology</title><idno type="eISSN">2399-3642</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and <italic>Drosophila</italic> protein modelling to show that Wnt5a is a direct ligand of toll-like receptor (TLR) 2 and 4. The binding promotes a MyD88-non-canonical nuclear factor of kappa B (NFκB) and AP-1 signalling cascade, with contradictory profiles in mouse (pro-inflammatory) and human (anti-inflammatory) myeloid immune cells. These data reveal that the true nature of Wnt5a in inflammatory cells, is to regulate TLR signals, and in human myeloid cells it acts as an endogenous, tolerance-associated molecular pattern (TAMP), inducing IL-10 and innate immune tolerance.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Shalapour, S" uniqKey="Shalapour S">S Shalapour</name></author><author><name sortKey="Karin, M" uniqKey="Karin M">M Karin</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Boomer, Js" uniqKey="Boomer J">JS Boomer</name></author><author><name sortKey="Green, Jm" uniqKey="Green J">JM Green</name></author><author><name sortKey="Hotchkiss, Rs" uniqKey="Hotchkiss R">RS Hotchkiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pereira, C" uniqKey="Pereira C">C Pereira</name></author><author><name sortKey="Schaer, Dj" uniqKey="Schaer D">DJ 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sortKey="Dionne, Ms" uniqKey="Dionne M">MS Dionne</name></author><author><name sortKey="Schneider, Ds" uniqKey="Schneider D">DS Schneider</name></author><author><name sortKey="Nusse, R" uniqKey="Nusse R">R Nusse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reynier, F" uniqKey="Reynier F">F Reynier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barrett, T" uniqKey="Barrett T">T Barrett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ibrahim, Za" uniqKey="Ibrahim Z">ZA Ibrahim</name></author><author><name sortKey="Armour, Cl" uniqKey="Armour C">CL Armour</name></author><author><name sortKey="Phipps, S" uniqKey="Phipps S">S Phipps</name></author><author><name sortKey="Sukkar, Mb" uniqKey="Sukkar M">MB Sukkar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kato, A" uniqKey="Kato A">A Kato</name></author><author><name sortKey="Ogasawara, T" uniqKey="Ogasawara T">T Ogasawara</name></author><author><name sortKey="Homma, T" uniqKey="Homma T">T Homma</name></author><author><name sortKey="Saito, H" uniqKey="Saito H">H Saito</name></author><author><name sortKey="Matsumoto, K" uniqKey="Matsumoto K">K Matsumoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dejmek, J" uniqKey="Dejmek J">J Dejmek</name></author><author><name sortKey="Safholm, A" uniqKey="Safholm A">A Safholm</name></author><author><name sortKey="Kamp Nielsen, C" uniqKey="Kamp Nielsen C">C Kamp Nielsen</name></author><author><name sortKey="Andersson, T" uniqKey="Andersson T">T Andersson</name></author><author><name sortKey="Leandersson, K" uniqKey="Leandersson K">K Leandersson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mancino, A" uniqKey="Mancino A">A Mancino</name></author><author><name sortKey="Lawrence, T" uniqKey="Lawrence T">T 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Wu</name></author><author><name sortKey="Siegel, Mi" uniqKey="Siegel M">MI Siegel</name></author><author><name sortKey="Egan, Rw" uniqKey="Egan R">RW Egan</name></author><author><name sortKey="Billah, Mm" uniqKey="Billah M">MM Billah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hedrich, Cm" uniqKey="Hedrich C">CM Hedrich</name></author><author><name sortKey="Bream, Jh" uniqKey="Bream J">JH Bream</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Yc" uniqKey="Chang Y">YC Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leandersson, K" uniqKey="Leandersson K">K Leandersson</name></author><author><name sortKey="Riesbeck, K" uniqKey="Riesbeck K">K Riesbeck</name></author><author><name sortKey="Andersson, T" uniqKey="Andersson T">T Andersson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vandesompele, J" uniqKey="Vandesompele J">J Vandesompele</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shevchenko, A" uniqKey="Shevchenko A">A Shevchenko</name></author><author><name sortKey="Tomas, H" uniqKey="Tomas H">H Tomas</name></author><author><name sortKey="Havlis, J" uniqKey="Havlis J">J Havlis</name></author><author><name sortKey="Olsen, Jv" uniqKey="Olsen J">JV Olsen</name></author><author><name sortKey="Mann, M" uniqKey="Mann M">M Mann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaudhury, S" uniqKey="Chaudhury S">S Chaudhury</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Suède</li></country></list><tree><country name="Suède"><noRegion><name sortKey="Mehmeti, Meliha" sort="Mehmeti, Meliha" uniqKey="Mehmeti M" first="Meliha" last="Mehmeti">Meliha Mehmeti</name></noRegion><name sortKey="Andre, Ingemar" sort="Andre, Ingemar" uniqKey="Andre I" first="Ingemar" last="André">Ingemar André</name><name sortKey="Bergenfelz, Caroline" sort="Bergenfelz, Caroline" uniqKey="Bergenfelz C" first="Caroline" last="Bergenfelz">Caroline Bergenfelz</name><name sortKey="Bergenfelz, Caroline" sort="Bergenfelz, Caroline" uniqKey="Bergenfelz C" first="Caroline" last="Bergenfelz">Caroline Bergenfelz</name><name sortKey="Bjork, Per" sort="Bjork, Per" uniqKey="Bjork P" first="Per" last="Björk">Per Björk</name><name sortKey="Ivars, Fredrik" sort="Ivars, Fredrik" uniqKey="Ivars F" first="Fredrik" last="Ivars">Fredrik Ivars</name><name sortKey="Johansson Lindbom, Bengt" sort="Johansson Lindbom, Bengt" uniqKey="Johansson Lindbom B" first="Bengt" last="Johansson-Lindbom">Bengt Johansson-Lindbom</name><name sortKey="K Llberg, Eva" sort="K Llberg, Eva" uniqKey="K Llberg E" first="Eva" last="K Llberg">Eva K Llberg</name><name sortKey="K Llberg, Eva" sort="K Llberg, Eva" uniqKey="K Llberg E" first="Eva" last="K Llberg">Eva K Llberg</name><name sortKey="Kjellstrom, Sven" sort="Kjellstrom, Sven" uniqKey="Kjellstrom S" first="Sven" last="Kjellström">Sven Kjellström</name><name sortKey="Leandersson, Karin" sort="Leandersson, Karin" uniqKey="Leandersson K" first="Karin" last="Leandersson">Karin Leandersson</name><name sortKey="Millrud, Camilla Rydberg" sort="Millrud, Camilla Rydberg" uniqKey="Millrud C" first="Camilla Rydberg" last="Millrud">Camilla Rydberg Millrud</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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