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Noncanonical immuno...
Noncanonical immunomodulatory activity of complement regulator C4BP(β-) limits the development of lupus nephritis
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- Luque, Ana (författare)
- L'Hospitalet de Llobregat, Barcelona,Bellvitge Biomedical Research Institute
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- Serrano, Inmaculada (författare)
- L'Hospitalet de Llobregat, Barcelona,Bellvitge Biomedical Research Institute
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- Ripoll, Elia (författare)
- Bellvitge University Hospital-IDIBELL,University of Barcelona
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- Malta, Catarina (författare)
- Bellvitge Biomedical Research Institute,L'Hospitalet de Llobregat, Barcelona
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- Gomà, Montserrat (författare)
- Bellvitge University Hospital-IDIBELL
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- Blom, Anna M. (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Grinyó, Josep M. (författare)
- University of Barcelona,Bellvitge University Hospital-IDIBELL
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- Rodríguez de Córdoba, Santiago (författare)
- Biological Research Center (CIB), Madrid
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- Torras, Joan (författare)
- University of Barcelona,Bellvitge University Hospital-IDIBELL
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- Aran, Josep M. (författare)
- L'Hospitalet de Llobregat, Barcelona,Bellvitge Biomedical Research Institute
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- Engelska 16 s.
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538. ; 97:3, s. 551-566
- Relaterad länk:
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http://dx.doi.org/10...
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http://diposit.ub.ed...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- C4BP(β−)
- dendritic cells
- ectopic lymphoid structures
- immunomodulation
- inflammation
- lupus nephritis
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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