Sökning: WFRF:(Mitjavila Francesca)
> (2022) >
The Hidden Side of ...
The Hidden Side of Complement Regulator C4BP : Dissection and Evaluation of Its Immunomodulatory Activity
-
- Serrano, Inmaculada (författare)
- Bellvitge University Hospital-IDIBELL
-
- Luque, Ana (författare)
- Bellvitge University Hospital-IDIBELL
-
- Mitjavila, Francesca (författare)
- Bellvitge University Hospital-IDIBELL
-
visa fler...
-
- Blom, Anna M. (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Department of Translational Medicine,Faculty of Medicine,Protein Chemistry, Malmö,Lund University Research Groups
-
- Rodríguez de Córdoba, Santiago (författare)
- CSIC Spanish National Research Council
-
- Vega, M. Cristina (författare)
- CSIC Spanish National Research Council
-
- Torras, Joan (författare)
- Bellvitge University Hospital-IDIBELL
-
- Aran, Josep M. (författare)
- Bellvitge University Hospital-IDIBELL
-
visa färre...
-
(creator_code:org_t)
- 2022-04-25
- 2022
- Engelska.
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
- Relaterad länk:
-
http://dx.doi.org/10... (free)
-
visa fler...
-
https://lup.lub.lu.s...
-
https://doi.org/10.3...
-
visa färre...
Abstract
Ämnesord
Stäng
- C4b-binding protein (C4BP) is a well-known regulator of the complement system that holds additional and important activities unrelated to complement inhibition. Recently, we have described a novel immunomodulatory activity in the minor C4BP(β-) isoform directly acting over inflammatory phagocytes. Here we show that incorporation of the β-chain to the C4BP α-chain oligomer interferes with this immunomodulatory activity of C4BP. Moreover, an oligomeric form including only the complement control protein 6 (CCP6) domain of the C4BP α-chain (PRP6-HO7) is sufficient to “reprogram” monocyte-derived DCs (Mo-DCs) from a pro-inflammatory and immunogenic phenotype to an anti-inflammatory and tolerogenic state. PRP6-HO7 lacks complement regulatory activity but retains full immunomodulatory activity over inflammatory Mo-DCs induced by TLRs, characterized by downregulation of relevant surface markers such as CD83, HLA-DR, co-stimulatory molecules such as CD86, CD80 and CD40, and pro-inflammatory cytokines such as IL-12 and TNF-α. Furthermore, PRP6-HO7-treated Mo-DCs shows increased endocytosis, significantly reduced CCR7 expression and CCL21-mediated chemotaxis, and prevents T cell alloproliferation. Finally, PRP6-HO7 shows also full immunomodulatory activity over Mo-DCs isolated from lupus nephritis patients with active disease, even without further pro-inflammatory stimulation. Therefore PRP6-HO7, retaining the immunomodulatory activity of C4BP(β-) and lacking its complement regulatory activity, might represent a promising and novel alternative to treat autoimmune diseases.
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
- immunomodulation
- inflammation
- lupus nephritis
- PRP6-HO7
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas