Details

Autor(en) / Beteiligte

• Desbois, A. C.
• Régnier, P.
• Quiniou, V.
• Lejoncour, A.
• Maciejewski‐Duval, A.
• Comarmond, C.
• Vallet, H.
• Rosenzwag, M.
• Darrasse‐Jèze, G.
• Derian, N.
• Pouchot, J.
• Samson, M.
• Bienvenu, B.
• Fouret, P.
• Koskas, F.
• Garrido, M.
• Sène, D.
• Bruneval, P.
• Cacoub, P.
• Klatzmann, D.
• Saadoun, D.

Titel

Specific Follicular Helper T Cell Signature in Takayasu Arteritis

Ist Teil von

• Arthritis & rheumatology (Hoboken, N.J.), 2021-07, Vol.73 (7), p.1233-1243

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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.