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The alpha(7)beta(0)...
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Olivar, RutL'Hospitalet de Llobregat, Barcelona
(författare)
The alpha(7)beta(0) Isoform of the Complement Regulator C4b-Binding Protein Induces a Semimature, Anti-Inflammatory State in Dendritic Cells
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
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2013-03-15
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The American Association of Immunologists,2013
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:3c541258-629c-49ad-9fa2-54e5d7ff0565
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https://lup.lub.lu.se/record/3651236URI
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https://doi.org/10.4049/jimmunol.1200503DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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The classical pathway complement regulator C4b-binding protein (C4BP) is composed of two polypeptides (alpha- and beta-chains), which form three plasma oligomers with different subunit compositions (alpha(7)beta(1), alpha(7)beta(0), and alpha(6)beta(1)). We show in this article that the C4BP alpha(7)beta(0) isoform (hereafter called C4BP[beta(-)] [C4BP lacking the beta-chain]), overexpressed under acute-phase conditions, induces a semimature, tolerogenic state on human monocyte-derived dendritic cells (DCs) activated by a proinflammatory stimulus. C4BP isoforms containing beta-chain (alpha(7)beta(1) and alpha(6)beta(1); C4BP[beta(+)]) neither interfered with the normal maturation of DCs nor competed with C4BP(beta(-)) activity on these cells. Immature DCs (iDCs) treated with C4BP(beta(-)) retained high endocytic activity, but, upon LPS treatment, they did not upregulate surface expression of CD83, CD80, and CD86. Transcriptional profiling of these semimature DCs revealed that treatment with C4BP(beta(-)) prevented the induction of IDO and BIC-1, whereas TGF-beta 1 expression was maintained to the level of iDCs. C4BP(beta(-))-treated DCs were also unable to release proinflammatory Th1 cytokines (IL-12, TNF-alpha, IFN-gamma, IL-6, IL-8) and, conversely, increased IL-10 secretion. They prevented surface CCR7 overexpression and, accordingly, displayed reduced chemotaxis, being morphologically indistinguishable from iDCs. Moreover, C4BP(beta(-))-treated DCs failed to enhance allogeneic T cell proliferation, impairing IFN-gamma production in these cells and, conversely, promoting CD4(+)CD127(low/neg) CD25(high)Foxp3(+) T cells. Deletion mutant analysis revealed that the complement control protein-6 domain of the alpha-chain is necessary for the tolerogenic activity of C4BP(beta(-)). Our data demonstrate a novel anti-inflammatory and immunomodulatory function of the complement regulator C4BP, suggesting a relevant role of the acute-phase C4BP(beta(-)) isoform in a number of pathophysiological conditions and potential applications in autoimmunity and transplantation. The Journal of Immunology, 2013, 190: 2857-2872.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Luque, AnaL'Hospitalet de Llobregat, Barcelona
(författare)
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Naranjo-Gomez, MarAutonomous University of Barcelona
(författare)
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Quer, JosepAutonomous University of Barcelona
(författare)
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Garcia de Frutos, PabloInstitutd' Investigacions Biomèdiques August Pi iSunyer (IDIBAPS)(Swepub:lu)klke-pga
(författare)
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Borras, Francesc E.Autonomous University of Barcelona
(författare)
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Rodriguez de Cordoba, Santiago
(författare)
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Blom, AnnaLund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-abl
(författare)
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Aran, Josep M.L'Hospitalet de Llobregat, Barcelona
(författare)
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L'Hospitalet de Llobregat, BarcelonaAutonomous University of Barcelona
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Immunology: The American Association of Immunologists190:6, s. 2857-28721550-66060022-1767
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