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Noncanonical immuno...
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Luque, AnaL'Hospitalet de Llobregat, Barcelona,Bellvitge Biomedical Research Institute
(författare)
Noncanonical immunomodulatory activity of complement regulator C4BP(β-) limits the development of lupus nephritis
- Artikel/kapitelEngelska2020
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Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:8810b55c-d0d9-467f-b719-70a640095629
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https://lup.lub.lu.se/record/8810b55c-d0d9-467f-b719-70a640095629URI
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https://doi.org/10.1016/j.kint.2019.10.016DOI
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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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Lupus nephritis is a chronic autoimmune-inflammatory condition that can lead to end-stage kidney disease. Presently available immunosuppressive treatments for lupus nephritis are suboptimal and can induce significant side effects. Recently, we characterized a novel immunomodulatory activity of the minor isoform of the classical pathway complement inhibitor, C4BP(β-). We show here that C4BP(β-) treatment prevented the development of proteinuria and albuminuria, decreased significantly the formation of anti-dsDNA antibodies and, locally, mitigated renal glomerular IgG and C3 deposition and generation of apoptotic cells. There was a consequent histological improvement and increased survival in lupus-prone mice. The therapeutic efficacy of C4BP(β-) was analogous to that of the broad-acting immunosuppressant cyclophosphamide. Remarkably, a comparative transcriptional profiling analysis revealed that the kidney gene expression signature resulting from C4BP(β-) treatment turned out to be 10 times smaller than that induced by cyclophosphamide treatment. C4BP(β-) immunomodulation induced significant downregulation of transcripts relevant to lupus nephritis indicating immunopathogenic cell infiltration, including activated T cells (Lat), B cells (Cd19, Ms4a1, Tnfrsf13c), inflammatory phagocytes (Irf7) and neutrophils (Prtn3, S100a8, S100a9). Furthermore, cytokine profiling and immunohistochemistry confirmed that C4BP(β-), through systemic and local CXCL13 downregulation, was able to prevent ectopic lymphoid structures neogenesis in aged mice with lupus nephritis. Thus, due to its anti-inflammatory and immunomodulatory activities and high specificity, C4BP(β-) could be considered for further clinical development in patients with systemic lupus erythematosus.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Serrano, InmaculadaL'Hospitalet de Llobregat, Barcelona,Bellvitge Biomedical Research Institute
(författare)
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Ripoll, EliaBellvitge University Hospital-IDIBELL,University of Barcelona
(författare)
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Malta, CatarinaBellvitge Biomedical Research Institute,L'Hospitalet de Llobregat, Barcelona
(författare)
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Gomà, MontserratBellvitge University Hospital-IDIBELL
(författare)
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Blom, Anna M.Lund 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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Grinyó, Josep M.University of Barcelona,Bellvitge University Hospital-IDIBELL
(författare)
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Rodríguez de Córdoba, SantiagoBiological Research Center (CIB), Madrid
(författare)
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Torras, JoanUniversity of Barcelona,Bellvitge University Hospital-IDIBELL
(författare)
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Aran, Josep M.L'Hospitalet de Llobregat, Barcelona,Bellvitge Biomedical Research Institute
(författare)
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L'Hospitalet de Llobregat, BarcelonaBellvitge Biomedical Research Institute
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Kidney International: Elsevier BV97:3, s. 551-5660085-2538
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