Specific Follicular Helper T Cell Signature in Takayasu Arteritis
| العنوان: | Specific Follicular Helper T Cell Signature in Takayasu Arteritis |
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| المؤلفون: | A.C. Desbois, Boris Bienvenu, Nicolas Dérian, Valentin Quiniou, M Rosenzwag, David Klatzmann, P Bruneval, Maxime Samson, David Saadoun, H. Vallet, Anna Maciejewski-Duval, Cloé Comarmond, Pierre Fouret, Damien Sène, Jacques Pouchot, Fabien Koskas, P. Régnier, G. Darrasse-Jèze, A Lejoncour, Marlène Garrido, Patrice Cacoub |
| المصدر: | Arthritis & Rheumatology. 73:1233-1243 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, CD4-Positive T-Lymphocytes, Male, Receptors, CXCR5, 0301 basic medicine, T Follicular Helper Cells, Receptors, Antigen, T-Cell, alpha-beta, Antigens, CD19, Giant Cell Arteritis, Programmed Cell Death 1 Receptor, Immunology, C-C chemokine receptor type 6, CXCR3, CD19, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Nitriles, Humans, Janus Kinase Inhibitors, Immunology and Allergy, Aorta, Aged, Cell Proliferation, Aged, 80 and over, 030203 arthritis & rheumatology, CD20, B-Lymphocytes, biology, Gene Expression Profiling, T-cell receptor, Middle Aged, Antigens, CD20, Takayasu Arteritis, CCL20, Pyrimidines, Tertiary Lymphoid Structures, 030104 developmental biology, Immunoglobulin G, biology.protein, Pyrazoles, Female, Antibody, Transcriptome, Immunologic Memory |
| الوصف: | OBJECTIVE Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. METHODS Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. RESULTS Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up-regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3- Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/β TCR repertoire. CONCLUSION We established the presence of a specific Tfh cell signature in both circulating and aorta-infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK. |
| تدمد: | 2326-5205 2326-5191 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::76692d042d6cf40de5cf9b41f4eefd2eTest https://doi.org/10.1002/art.41672Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....76692d042d6cf40de5cf9b41f4eefd2e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23265205 23265191 |
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