Alessia Alunno1, Lidia Ibba-Manneschi2, Onelia Bistoni1, Sabrina Cipriani1, Fabiana Topini1, Roberto Gerli1, Mirko Manetti3. 1. Rheumatology Unit, Department of Medicine, University of Perugia, Italy. 2. Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Italy. 3. Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Italy. mirko.manetti@unifi.it.
Abstract
OBJECTIVES: The mechanisms underlying increased cardiovascular risk in primary Sjögren's syndrome (pSS) remain unclear. Since the recently discovered angiogenic T cells (Tang) may participate in endothelial repair by cooperating with endothelial progenitor cells (EPC), we aimed to quantify and characterise Tang in the peripheral blood and minor salivary glands (MSG) of pSS patients. METHODS: Tang (CD3+CD31+CXCR4+) and EPC (CD34+CD133+VEGFR-2+) were quantified by flow cytometry in peripheral blood samples from 36 pSS patients and 20 healthy donors. Tang subsets were assessed on the basis of CD4, CD8 and CD28 expression. Labial MSG sections from 10 pSS patients and 12 non-pSS sicca syndrome controls were subjected to immunofluorescence staining to investigate the presence of Tang and the expression of the CXCR4-ligand stromal cell-derived factor-1 (SDF-1)/CXCL12. RESULTS: Circulating Tang cells were expanded and directly correlated to EPC in pSS. Both Tang and EPC directly correlated with disease activity as calculated with the EULAR Sjögren's syndrome disease activity index (ESSDAI). In pSS, the majority of Tang cells were CD4-CD8- double negative (DN) and lacked CD28 revealing a senescent phenotype. A subset of CD4+, CD8+ and DN Tang cells produced interleukin-17. Immunohistology revealed the exclusive presence of periductal and perivascular infiltrating Tang cells along with increased SDF-1/CXCL12 expression in pSS MSG compared to non-pSS sicca syndrome controls. CONCLUSIONS: In pSS, Tang cells are expanded in peripheral blood and infiltrate MSG. Tang may be novel actors in pSS-related endothelial dysfunction and glandular neo-angiogenesis and inflammation.
OBJECTIVES: The mechanisms underlying increased cardiovascular risk in primary Sjögren's syndrome (pSS) remain unclear. Since the recently discovered angiogenic T cells (Tang) may participate in endothelial repair by cooperating with endothelial progenitor cells (EPC), we aimed to quantify and characterise Tang in the peripheral blood and minor salivary glands (MSG) of pSSpatients. METHODS: Tang (CD3+CD31+CXCR4+) and EPC (CD34+CD133+VEGFR-2+) were quantified by flow cytometry in peripheral blood samples from 36 pSSpatients and 20 healthy donors. Tang subsets were assessed on the basis of CD4, CD8 and CD28 expression. Labial MSG sections from 10 pSSpatients and 12 non-pSS sicca syndrome controls were subjected to immunofluorescence staining to investigate the presence of Tang and the expression of the CXCR4-ligand stromal cell-derived factor-1 (SDF-1)/CXCL12. RESULTS: Circulating Tang cells were expanded and directly correlated to EPC in pSS. Both Tang and EPC directly correlated with disease activity as calculated with the EULAR Sjögren's syndrome disease activity index (ESSDAI). In pSS, the majority of Tang cells were CD4-CD8- double negative (DN) and lacked CD28 revealing a senescent phenotype. A subset of CD4+, CD8+ and DN Tang cells produced interleukin-17. Immunohistology revealed the exclusive presence of periductal and perivascular infiltrating Tang cells along with increased SDF-1/CXCL12 expression in pSS MSG compared to non-pSS sicca syndrome controls. CONCLUSIONS: In pSS, Tang cells are expanded in peripheral blood and infiltrate MSG. Tang may be novel actors in pSS-related endothelial dysfunction and glandular neo-angiogenesis and inflammation.
Authors: Fabiola Atzeni; Francesco Gozza; Giacomo Cafaro; Carlo Perricone; Elena Bartoloni Journal: Front Immunol Date: 2022-05-06 Impact factor: 8.786
Authors: Verónica Pulito-Cueto; Sara Remuzgo-Martínez; Fernanda Genre; Belén Atienza-Mateo; Víctor M Mora-Cuesta; David Iturbe-Fernández; Leticia Lera-Gómez; Javier Rodriguez-Carrio; Diana Prieto-Peña; Virginia Portilla; Ricardo Blanco; Alfonso Corrales; Oreste Gualillo; José M Cifrián; Raquel López-Mejías; Miguel A González-Gay Journal: Biomedicines Date: 2022-04-05
Authors: Jolien F van Nimwegen; Karin van der Tuuk; Silvia C Liefers; Gwenny M Verstappen; Annie Visser; Robin F Wijnsma; Arjan Vissink; Harry Hollema; Marian J E Mourits; Hendrika Bootsma; Frans G M Kroese Journal: Rheumatology (Oxford) Date: 2020-10-01 Impact factor: 7.580