We previously reported that a synthetic peptide with sequence identical to a CDR of a mouse monoclonal antibody specific for difucosyl human blood group A exerted an immunomodulatory activity on murine macrophages. It was therapeutic against systemic candidiasis without possessing direct candidacidal properties. Here we demonstrate that a selected peptide, N10K, putatively deriving from the enzymatic cleavage of the constant region (Fc) of human IgG(1), is able to induce IL-6 secretion and pIkB-α activation. More importantly, it causes an up-regulation of Dectin-1 expression. This leads to an increased activation of β-glucan-induced pSyk, CARD9 and pIkB-α, and an increase in the production of pro-inflammatory cytokines such as IL-6, IL-12, IL-1β and TNF-α. The increased activation of this pathway coincides with an augmented phagocytosis of non opsonized Candida albicans cells by monocytes. The findings suggest that some Fc-peptides, potentially deriving from the proteolysis of immunoglobulins, may cause an unexpected immunoregulation in a way reminiscent of innate immunity molecules

Antibody Constant Region Peptides Can Display Immunomodulatory Activity through Activation of the Dectin-1 Signalling Pathway / Gabrielli, E; Pericolini, Eva; Cenci, E; Monari, C; Magliani, W; Ciociola, T; Conti, S; Gatti, R; Bistoni, F; Polonelli, L; Vecchiarelli, A.. - In: PLOS ONE. - ISSN 1932-6203. - 7:8(2012), pp. 1-12. [10.1371/journal.pone.0043972]

Antibody Constant Region Peptides Can Display Immunomodulatory Activity through Activation of the Dectin-1 Signalling Pathway

PERICOLINI, Eva;
2012

Abstract

We previously reported that a synthetic peptide with sequence identical to a CDR of a mouse monoclonal antibody specific for difucosyl human blood group A exerted an immunomodulatory activity on murine macrophages. It was therapeutic against systemic candidiasis without possessing direct candidacidal properties. Here we demonstrate that a selected peptide, N10K, putatively deriving from the enzymatic cleavage of the constant region (Fc) of human IgG(1), is able to induce IL-6 secretion and pIkB-α activation. More importantly, it causes an up-regulation of Dectin-1 expression. This leads to an increased activation of β-glucan-induced pSyk, CARD9 and pIkB-α, and an increase in the production of pro-inflammatory cytokines such as IL-6, IL-12, IL-1β and TNF-α. The increased activation of this pathway coincides with an augmented phagocytosis of non opsonized Candida albicans cells by monocytes. The findings suggest that some Fc-peptides, potentially deriving from the proteolysis of immunoglobulins, may cause an unexpected immunoregulation in a way reminiscent of innate immunity molecules
2012
7
8
1
12
Antibody Constant Region Peptides Can Display Immunomodulatory Activity through Activation of the Dectin-1 Signalling Pathway / Gabrielli, E; Pericolini, Eva; Cenci, E; Monari, C; Magliani, W; Ciociola, T; Conti, S; Gatti, R; Bistoni, F; Polonelli, L; Vecchiarelli, A.. - In: PLOS ONE. - ISSN 1932-6203. - 7:8(2012), pp. 1-12. [10.1371/journal.pone.0043972]
Gabrielli, E; Pericolini, Eva; Cenci, E; Monari, C; Magliani, W; Ciociola, T; Conti, S; Gatti, R; Bistoni, F; Polonelli, L; Vecchiarelli, A.
File in questo prodotto:
File Dimensione Formato  
Gabrielli E. et al. 2012 PLoS ONE Antibody constant region....pdf

Open access

Descrizione: Gabrielli E., PLOS ONE 2012
Tipologia: Versione pubblicata dall'editore
Dimensione 1.36 MB
Formato Adobe PDF
1.36 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1120029
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 16
social impact