Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis

Francesco Ciccia, Aroldo Rizzo, Rosario Maugeri, Riccardo Alessandro, Stefania Croci, Giuliana Guggino, Alberto Cavazza, Stefania Raimondo, Alessandra Cannizzaro, Domenico Gerardo Iacopino, Carlo Salvarani, Giovanni Triolo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objectives To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Methods Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. Results ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-ß, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. Conclusions ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.

Original languageEnglish
JournalAnnals of the Rheumatic Diseases
DOIs
Publication statusAccepted/In press - Apr 20 2016

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Lymphotoxin-alpha
Giant Cell Arteritis
Arteries
Toll-Like Receptors
Cytokines
Ligands
Chemokines
B-Cell Activating Factor
Follicular Dendritic Cells
Tissue
Interleukin-7
Myofibroblasts
Interleukin-17
Chemokine Receptors
RNA-Directed DNA Polymerase
Lymphoid Tissue
Antigens
Temporal Arteries
Venules
Helper-Inducer T-Lymphocytes

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis. / Ciccia, Francesco; Rizzo, Aroldo; Maugeri, Rosario; Alessandro, Riccardo; Croci, Stefania; Guggino, Giuliana; Cavazza, Alberto; Raimondo, Stefania; Cannizzaro, Alessandra; Iacopino, Domenico Gerardo; Salvarani, Carlo; Triolo, Giovanni.

In: Annals of the Rheumatic Diseases, 20.04.2016.

Research output: Contribution to journalArticle

Ciccia, Francesco ; Rizzo, Aroldo ; Maugeri, Rosario ; Alessandro, Riccardo ; Croci, Stefania ; Guggino, Giuliana ; Cavazza, Alberto ; Raimondo, Stefania ; Cannizzaro, Alessandra ; Iacopino, Domenico Gerardo ; Salvarani, Carlo ; Triolo, Giovanni. / Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis. In: Annals of the Rheumatic Diseases. 2016.
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title = "Ectopic expression of CXCL13, BAFF, APRIL and LT-{\ss} is associated with artery tertiary lymphoid organs in giant cell arteritis",
abstract = "Objectives To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Methods Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. Results ATLOs were observed in the media layer of 60{\%} of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-{\ss}, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. Conclusions ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.",
author = "Francesco Ciccia and Aroldo Rizzo and Rosario Maugeri and Riccardo Alessandro and Stefania Croci and Giuliana Guggino and Alberto Cavazza and Stefania Raimondo and Alessandra Cannizzaro and Iacopino, {Domenico Gerardo} and Carlo Salvarani and Giovanni Triolo",
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T1 - Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis

AU - Ciccia, Francesco

AU - Rizzo, Aroldo

AU - Maugeri, Rosario

AU - Alessandro, Riccardo

AU - Croci, Stefania

AU - Guggino, Giuliana

AU - Cavazza, Alberto

AU - Raimondo, Stefania

AU - Cannizzaro, Alessandra

AU - Iacopino, Domenico Gerardo

AU - Salvarani, Carlo

AU - Triolo, Giovanni

PY - 2016/4/20

Y1 - 2016/4/20

N2 - Objectives To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Methods Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. Results ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-ß, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. Conclusions ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.

AB - Objectives To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Methods Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. Results ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-ß, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. Conclusions ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.

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JO - Annals of the Rheumatic Diseases

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