Interleukin-25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome

Francesco Ciccia, Giovanni Triolo, Giuseppina Candore, Francesco Dieli, Giuliana Guggino, Riccardo Alessandro, Laura Saieva, Stefania Raimondo, Xiang Lin, Aroldo Rizzo, Piero Ruscitti, Fan Xiao, Roberto Giacomelli, Paola Cipriani, Liwei Lu, Diana Di Liberto

Risultato della ricerca: Article

7 Citazioni (Scopus)

Abstract

Objective: To investigate the role of the interleukin-25 (IL-25)/IL-17 receptor B (IL-17RB) axis in experimental Sjögren's syndrome (SS) and in patients with primary SS and primary SS–associated lymphoma. Methods: Expression of IL-25, IL-17RB, IL-17B, and tumor necrosis factor receptor–associated factor 6 (TRAF6) was analyzed on minor salivary gland (SG) samples from patients with primary SS and on parotid gland samples from patients with primary SS–associated B cell non-Hodgkin's lymphoma (NHL). IL-17RB expression and the frequencies of natural group 2 innate lymphoid cells (ILC2s), inflammatory ILC2s, and M2-polarized macrophages were assessed by flow cytometry in SG mononuclear cells and peripheral blood mononuclear cells (PBMCs). Tissue distribution of ILC2s was studied by confocal microscopy. The role of recombinant IL-25 and of rituximab in modulating IL-25 expression was investigated in in vitro studies. IL-25/IL-17RB and TRAF6 expression and the role of IL-25 inhibition were also studied in the experimental murine model of SS. Results: Activation of the IL-25/IL-17RB/TRAF6 axis correlated with the focus score and was observed in patients with primary SS and in patients with primary SS–associated NHL. A significant increase in the frequency of inflammatory ILC2s was observed both in SG mononuclear cells and in PBMCs. IL-25 stimulation of isolated SG mononuclear cells and PBMCs from patients and controls resulted both in inflammatory ILC2 expansion and in increased autoantibody production. Rituximab modulated expression of inflammatory ILC2s and IL-25 in primary SS. SG protein–immunized mice developed overt SS symptoms with increased IL-25 expression and increased frequency of CD4+IL-17RB+TRAF6+ cells. IL-25 neutralization attenuated disease progression and tissue pathology in mice with experimental SS. Conclusion: IL-25 may promote the inflammatory state in primary SS and may be a potential target for novel disease-modifying therapeutic strategies in patients with primary SS.
Lingua originaleEnglish
pagine (da-a)1265-1275
Numero di pagine11
RivistaARTHRITIS & RHEUMATOLOGY
Volume70
Stato di pubblicazionePublished - 2018

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Interleukin-17
Interleukin-17 Receptors
TNF Receptor-Associated Factor 6
Salivary Glands
Blood Cells
Non-Hodgkin's Lymphoma
Minor Salivary Glands
Parotid Gland
B-Cell Lymphoma
Tissue Distribution
Confocal Microscopy
Autoantibodies
Disease Progression
Lymphoma
Flow Cytometry
Theoretical Models
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cita questo

Interleukin-25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome. / Ciccia, Francesco; Triolo, Giovanni; Candore, Giuseppina; Dieli, Francesco; Guggino, Giuliana; Alessandro, Riccardo; Saieva, Laura; Raimondo, Stefania; Lin, Xiang; Rizzo, Aroldo; Ruscitti, Piero; Xiao, Fan; Giacomelli, Roberto; Cipriani, Paola; Lu, Liwei; Di Liberto, Diana.

In: ARTHRITIS & RHEUMATOLOGY, Vol. 70, 2018, pag. 1265-1275.

Risultato della ricerca: Article

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title = "Interleukin-25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sj{\"o}gren's Syndrome",
abstract = "Objective: To investigate the role of the interleukin-25 (IL-25)/IL-17 receptor B (IL-17RB) axis in experimental Sj{\"o}gren's syndrome (SS) and in patients with primary SS and primary SS–associated lymphoma. Methods: Expression of IL-25, IL-17RB, IL-17B, and tumor necrosis factor receptor–associated factor 6 (TRAF6) was analyzed on minor salivary gland (SG) samples from patients with primary SS and on parotid gland samples from patients with primary SS–associated B cell non-Hodgkin's lymphoma (NHL). IL-17RB expression and the frequencies of natural group 2 innate lymphoid cells (ILC2s), inflammatory ILC2s, and M2-polarized macrophages were assessed by flow cytometry in SG mononuclear cells and peripheral blood mononuclear cells (PBMCs). Tissue distribution of ILC2s was studied by confocal microscopy. The role of recombinant IL-25 and of rituximab in modulating IL-25 expression was investigated in in vitro studies. IL-25/IL-17RB and TRAF6 expression and the role of IL-25 inhibition were also studied in the experimental murine model of SS. Results: Activation of the IL-25/IL-17RB/TRAF6 axis correlated with the focus score and was observed in patients with primary SS and in patients with primary SS–associated NHL. A significant increase in the frequency of inflammatory ILC2s was observed both in SG mononuclear cells and in PBMCs. IL-25 stimulation of isolated SG mononuclear cells and PBMCs from patients and controls resulted both in inflammatory ILC2 expansion and in increased autoantibody production. Rituximab modulated expression of inflammatory ILC2s and IL-25 in primary SS. SG protein–immunized mice developed overt SS symptoms with increased IL-25 expression and increased frequency of CD4+IL-17RB+TRAF6+ cells. IL-25 neutralization attenuated disease progression and tissue pathology in mice with experimental SS. Conclusion: IL-25 may promote the inflammatory state in primary SS and may be a potential target for novel disease-modifying therapeutic strategies in patients with primary SS.",
author = "Francesco Ciccia and Giovanni Triolo and Giuseppina Candore and Francesco Dieli and Giuliana Guggino and Riccardo Alessandro and Laura Saieva and Stefania Raimondo and Xiang Lin and Aroldo Rizzo and Piero Ruscitti and Fan Xiao and Roberto Giacomelli and Paola Cipriani and Liwei Lu and {Di Liberto}, Diana",
year = "2018",
language = "English",
volume = "70",
pages = "1265--1275",
journal = "ARTHRITIS & RHEUMATOLOGY",
issn = "2326-5191",

}

TY - JOUR

T1 - Interleukin-25 Axis Is Involved in the Pathogenesis of Human Primary and Experimental Murine Sjögren's Syndrome

AU - Ciccia, Francesco

AU - Triolo, Giovanni

AU - Candore, Giuseppina

AU - Dieli, Francesco

AU - Guggino, Giuliana

AU - Alessandro, Riccardo

AU - Saieva, Laura

AU - Raimondo, Stefania

AU - Lin, Xiang

AU - Rizzo, Aroldo

AU - Ruscitti, Piero

AU - Xiao, Fan

AU - Giacomelli, Roberto

AU - Cipriani, Paola

AU - Lu, Liwei

AU - Di Liberto, Diana

PY - 2018

Y1 - 2018

N2 - Objective: To investigate the role of the interleukin-25 (IL-25)/IL-17 receptor B (IL-17RB) axis in experimental Sjögren's syndrome (SS) and in patients with primary SS and primary SS–associated lymphoma. Methods: Expression of IL-25, IL-17RB, IL-17B, and tumor necrosis factor receptor–associated factor 6 (TRAF6) was analyzed on minor salivary gland (SG) samples from patients with primary SS and on parotid gland samples from patients with primary SS–associated B cell non-Hodgkin's lymphoma (NHL). IL-17RB expression and the frequencies of natural group 2 innate lymphoid cells (ILC2s), inflammatory ILC2s, and M2-polarized macrophages were assessed by flow cytometry in SG mononuclear cells and peripheral blood mononuclear cells (PBMCs). Tissue distribution of ILC2s was studied by confocal microscopy. The role of recombinant IL-25 and of rituximab in modulating IL-25 expression was investigated in in vitro studies. IL-25/IL-17RB and TRAF6 expression and the role of IL-25 inhibition were also studied in the experimental murine model of SS. Results: Activation of the IL-25/IL-17RB/TRAF6 axis correlated with the focus score and was observed in patients with primary SS and in patients with primary SS–associated NHL. A significant increase in the frequency of inflammatory ILC2s was observed both in SG mononuclear cells and in PBMCs. IL-25 stimulation of isolated SG mononuclear cells and PBMCs from patients and controls resulted both in inflammatory ILC2 expansion and in increased autoantibody production. Rituximab modulated expression of inflammatory ILC2s and IL-25 in primary SS. SG protein–immunized mice developed overt SS symptoms with increased IL-25 expression and increased frequency of CD4+IL-17RB+TRAF6+ cells. IL-25 neutralization attenuated disease progression and tissue pathology in mice with experimental SS. Conclusion: IL-25 may promote the inflammatory state in primary SS and may be a potential target for novel disease-modifying therapeutic strategies in patients with primary SS.

AB - Objective: To investigate the role of the interleukin-25 (IL-25)/IL-17 receptor B (IL-17RB) axis in experimental Sjögren's syndrome (SS) and in patients with primary SS and primary SS–associated lymphoma. Methods: Expression of IL-25, IL-17RB, IL-17B, and tumor necrosis factor receptor–associated factor 6 (TRAF6) was analyzed on minor salivary gland (SG) samples from patients with primary SS and on parotid gland samples from patients with primary SS–associated B cell non-Hodgkin's lymphoma (NHL). IL-17RB expression and the frequencies of natural group 2 innate lymphoid cells (ILC2s), inflammatory ILC2s, and M2-polarized macrophages were assessed by flow cytometry in SG mononuclear cells and peripheral blood mononuclear cells (PBMCs). Tissue distribution of ILC2s was studied by confocal microscopy. The role of recombinant IL-25 and of rituximab in modulating IL-25 expression was investigated in in vitro studies. IL-25/IL-17RB and TRAF6 expression and the role of IL-25 inhibition were also studied in the experimental murine model of SS. Results: Activation of the IL-25/IL-17RB/TRAF6 axis correlated with the focus score and was observed in patients with primary SS and in patients with primary SS–associated NHL. A significant increase in the frequency of inflammatory ILC2s was observed both in SG mononuclear cells and in PBMCs. IL-25 stimulation of isolated SG mononuclear cells and PBMCs from patients and controls resulted both in inflammatory ILC2 expansion and in increased autoantibody production. Rituximab modulated expression of inflammatory ILC2s and IL-25 in primary SS. SG protein–immunized mice developed overt SS symptoms with increased IL-25 expression and increased frequency of CD4+IL-17RB+TRAF6+ cells. IL-25 neutralization attenuated disease progression and tissue pathology in mice with experimental SS. Conclusion: IL-25 may promote the inflammatory state in primary SS and may be a potential target for novel disease-modifying therapeutic strategies in patients with primary SS.

UR - http://hdl.handle.net/10447/295627

M3 - Article

VL - 70

SP - 1265

EP - 1275

JO - ARTHRITIS & RHEUMATOLOGY

JF - ARTHRITIS & RHEUMATOLOGY

SN - 2326-5191

ER -