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Specific Follicular Helper T Cell Signature in Takayasu Arteritis
Author(s) -
Desbois A. C.,
Régnier P.,
Quiniou V.,
Lejoncour A.,
MaciejewskiDuval A.,
Comarmond C.,
Vallet H.,
Rosenzwag M.,
DarrasseJèze 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.
Publication year - 2021
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41672
Subject(s) - c c chemokine receptor type 6 , immunophenotyping , cd19 , t cell , cxcr5 , interleukin 21 , immunology , biology , ccl20 , cxcr3 , cxcl16 , cxcl13 , b cell , naive b cell , giant cell arteritis , flow cytometry , antibody , inflammation , medicine , cxcl10 , antigen presenting cell , pathology , chemokine receptor , chemokine , vasculitis , immune system , germinal center , disease
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.