Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis
By Deepak A. Rao, M. Gurish, J. Marshall, Kamil Slowikowski, C. Fonseka, Yanyan Liu, L. Donlin, L. Henderson, Kevin Wei, F. Mizoguchi and 18 more. Nature, 2017
995 citations recorded by the source corpus.
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. 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. This approach revealed a markedly expanded population of PD-1hiCXCR5−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-1hiCXCR5− ‘peripheral helper’ T (TPH) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1hiCXCR5+ T follicular helper cells, TPH cells induce plasma cell differentiation in vitro through IL-21 secretion and SLAMF5 interaction (refs 3, 4). However, global transcriptomics highlight differences between TPH 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 TPH cells. TPH cells appear to be uniquely poised to promote B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/1622f1d0902b8cb42cceaee7901cc55e562342a5
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Citations in the corpus
- Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy (2019, background): “Cells in cluster #22 shared several genes with Tregs including TIGIT, BATF, ICA1 and TNFRSF4 (OX-40), but lacked Tregs-defining transcripts FOXP3, IL2RA, TNFRSF18 and IKZF2 (HELIOS) while they expressed high levels of CD40LG and the chemokine CXCL13, and thus were referred to as T follicular helper-”
- T follicular helper cell biology: A decade of discovery and diseases (2019, background): “These CXCL13+CXCR5negPD1+IL-21+ CD4+ T cells (Rao et al., 2017) appear to be related to the surprising CXCL13+CXCR5neg CD4+ T cells found in ELS of breast cancer (see below).”