Tuftsin-PhosphorylCholine (TPC) is a novel bi-specific molecule which links tuftsin and phosphorylcholine. TPC has shown immunomodulatory activities in experimental mouse models of autoimmune diseases. We studied herein the effects of TPC ex vivo on both peripheral blood mononuclear cells (PBMCs) and temporal artery biopsies (TABs) obtained from patients with giant cell arteritis (GCA) and age-matched disease controls. GCA is an immune-mediated disease affecting large vessels. Levels of 18 cytokines in supernatants, PBMC viability, T helper (Th) cell differentiation of PBMCs and gene expression in TABs were analyzed. Treatment ex vivo with TPC decreased the production of IL-1β, IL-2, IL-5, IL-6, IL-9, IL-12(p70), IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IFNγ, TNFα, GM-CSF by CD3/CD28 activated PBMCs whereas it negligibly affected cell viability. It reduced Th1 and Th17 differentiation while did not impact Th22 differentiation in PBMCs stimulated by phorbol 12-myristate 13-acetate plus ionomycin. In inflamed TABs, treatment with TPC down-regulated the production of IL-1β, IL-6, IL-13, IL-17A and CD68 gene expression. The effects of TPC were comparable to the effects of dexamethasone, included as the standard of care, with the exception of a greater reduction of IL-2, IL-18, IFNγ in CD3/CD28 activated PBMCs and CD68 gene in inflamed TABs. In conclusion our results warrant further investigations regarding TPC as an immunotherapeutic agent in GCA and potentially other autoimmune and inflammatory diseases.

The therapeutic potential of tuftsin-phosphorylcholine in giant cell arteritis / Croci, Stefania; Bonacini, Martina; Muratore, Francesco; Caruso, Andrea; Fontana, Antonio; Boiardi, Luigi; Soriano, Alessandra; Cavazza, Alberto; Cimino, Luca; Belloni, Lucia; Perry, Ori; Fridkin, Mati; Parmeggiani, Maria; Blank, Miri; Shoenfeld, Yehuda; Salvarani, Carlo. - In: JOURNAL OF AUTOIMMUNITY. - ISSN 0896-8411. - 98:(2019), pp. 113-121. [10.1016/j.jaut.2019.01.002]

The therapeutic potential of tuftsin-phosphorylcholine in giant cell arteritis

Muratore, Francesco;Cimino, Luca;Salvarani, Carlo
2019

Abstract

Tuftsin-PhosphorylCholine (TPC) is a novel bi-specific molecule which links tuftsin and phosphorylcholine. TPC has shown immunomodulatory activities in experimental mouse models of autoimmune diseases. We studied herein the effects of TPC ex vivo on both peripheral blood mononuclear cells (PBMCs) and temporal artery biopsies (TABs) obtained from patients with giant cell arteritis (GCA) and age-matched disease controls. GCA is an immune-mediated disease affecting large vessels. Levels of 18 cytokines in supernatants, PBMC viability, T helper (Th) cell differentiation of PBMCs and gene expression in TABs were analyzed. Treatment ex vivo with TPC decreased the production of IL-1β, IL-2, IL-5, IL-6, IL-9, IL-12(p70), IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IFNγ, TNFα, GM-CSF by CD3/CD28 activated PBMCs whereas it negligibly affected cell viability. It reduced Th1 and Th17 differentiation while did not impact Th22 differentiation in PBMCs stimulated by phorbol 12-myristate 13-acetate plus ionomycin. In inflamed TABs, treatment with TPC down-regulated the production of IL-1β, IL-6, IL-13, IL-17A and CD68 gene expression. The effects of TPC were comparable to the effects of dexamethasone, included as the standard of care, with the exception of a greater reduction of IL-2, IL-18, IFNγ in CD3/CD28 activated PBMCs and CD68 gene in inflamed TABs. In conclusion our results warrant further investigations regarding TPC as an immunotherapeutic agent in GCA and potentially other autoimmune and inflammatory diseases.
2019
10-gen-2019
98
113
121
The therapeutic potential of tuftsin-phosphorylcholine in giant cell arteritis / Croci, Stefania; Bonacini, Martina; Muratore, Francesco; Caruso, Andrea; Fontana, Antonio; Boiardi, Luigi; Soriano, Alessandra; Cavazza, Alberto; Cimino, Luca; Belloni, Lucia; Perry, Ori; Fridkin, Mati; Parmeggiani, Maria; Blank, Miri; Shoenfeld, Yehuda; Salvarani, Carlo. - In: JOURNAL OF AUTOIMMUNITY. - ISSN 0896-8411. - 98:(2019), pp. 113-121. [10.1016/j.jaut.2019.01.002]
Croci, Stefania; Bonacini, Martina; Muratore, Francesco; Caruso, Andrea; Fontana, Antonio; Boiardi, Luigi; Soriano, Alessandra; Cavazza, Alberto; Cimino, Luca; Belloni, Lucia; Perry, Ori; Fridkin, Mati; Parmeggiani, Maria; Blank, Miri; Shoenfeld, Yehuda; Salvarani, Carlo
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0896841118305493-main.pdf

Accesso riservato

Tipologia: Versione pubblicata dall'editore
Dimensione 1.13 MB
Formato Adobe PDF
1.13 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
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/11380/1176894
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 5
social impact