Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Rao, D., Gurish, M., Marshall, J., Slowikowski, K., Fonseka, C., Liu, Y., Donlin, L., Henderson, L., Wei, K., Mizoguchi, F., Teslovich, N., Weinblatt, M., Massarotti, E., Coblyn, J., Helfgott, S., Lee, Y., Todd, D., Bykerk, V., Goodman, S., Pernis, A., Ivashkiv, L., Karlson, E., Nigrovic, P., Filer, A., Buckley, C., Lederer, J., Raychaudhuri, S., & Brenner, M. Nature, 2017. abstract bibtex © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 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-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-1hi 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.
@article{
title = {Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis},
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year = {2017},
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abstract = {© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 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-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-1hi 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.},
bibtype = {article},
author = {Rao, D.A. and Gurish, M.F. and Marshall, J.L. and Slowikowski, K. and Fonseka, C.Y. and Liu, Y. and Donlin, L.T. and Henderson, L.A. and Wei, K. and Mizoguchi, F. and Teslovich, N.C. and Weinblatt, M.E. and Massarotti, E.M. and Coblyn, J.S. and Helfgott, S.M. and Lee, Y.C. and Todd, D.J. and Bykerk, V.P. and Goodman, S.M. and Pernis, A.B. and Ivashkiv, L.B. and Karlson, E.W. and Nigrovic, P.A. and Filer, A. and Buckley, C.D. and Lederer, J.A. and Raychaudhuri, S. and Brenner, M.B.},
journal = {Nature},
number = {7639}
}
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All rights reserved. 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-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-1hi CXCR5- peripheral helper' T (T PH) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. 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