Journal
NATURE
Volume 542, Issue 7639, Pages 110-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature20810
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Funding
- William Docken Inflammatory Autoimmune Disease Fund
- Mallinckrodt Research Fellowship
- NIH [5U01GM092691-05, 1U19 AI111224-01]
- Doris Duke Charitable Foundation [2013097]
- Rheumatology Research Foundation Scientist Development Award
- Arthritis Research UK [19791, 18547]
- Fundacion Bechara
- [T32 AR007530-31]
- [R01 AR064850-03]
- [K01 AR066063]
- [FP7-HEALTH-F2-2012-305549 EuroTEAM]
- [P30 AR070253]
- Versus Arthritis [19791, 20088] Funding Source: researchfish
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CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation(1). Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population(2). This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis. However, these cells are not exhausted, despite high PD-1 expression. Rather, using multidimensional cytometry, transcriptomics, and functional assays, we define a population of PD-1(hi)CXCR5(-) 'peripheral helper' T (T-PH) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1(hi)CXCR5(+) T follicular helper cells, T-PH cells induce plasma cell differentiation in vitro through IL-21 secretion and SLAMF5 interaction (refs 3, 4). However, global transcriptomics highlight differences between T-PH cells and T follicular helper cells, including altered expression of BCL6 and BLIMP1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in T-PH cells. T-PH cells appear to be uniquely poised to promote B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues.
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