Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis
CD4+ T cells are central mediators of autoimmune pathology; however, the definition of their key effector functions in specific autoimmune diseases remains limited. Pathogenic CD4+ T cells within affected tissues may be identified by expression of markers of recent activation1. We applied this appro...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Published: |
Nature Publishing Group
2017
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| _version_ | 1797058014085120000 |
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| author | Rao, DA Gurish, MF Marshall, JL Slowikowski, K Fonseka, CY Liu, Y Donlin, LT Henderson, LA Wei, K Mizoguchi, F Teslovich, NC Weinblatt, ME Massarotti, EM Coblyn, JS Helfgott, SM Lee, YC Todd, DJ Bykerk, VP Goodman, SM Pernis, AB Ivashkiv, LB Karlson, EW Nigrovic, PA Filer, A Buckley, CD Lederer, JA Raychaudhuri, S Brenner, MB |
| author_facet | Rao, DA Gurish, MF Marshall, JL Slowikowski, K Fonseka, CY Liu, Y Donlin, LT Henderson, LA Wei, K Mizoguchi, F Teslovich, NC Weinblatt, ME Massarotti, EM Coblyn, JS Helfgott, SM Lee, YC Todd, DJ Bykerk, VP Goodman, SM Pernis, AB Ivashkiv, LB Karlson, EW Nigrovic, PA Filer, A Buckley, CD Lederer, JA Raychaudhuri, S Brenner, MB |
| author_sort | Rao, DA |
| collection | OXFORD |
| description | CD4+ T cells are central mediators of autoimmune pathology; however, the definition of their key effector functions in specific autoimmune diseases remains limited. Pathogenic CD4+ T cells within affected tissues may be identified by expression of markers of recent activation1. We applied this approach to joint tissue in rheumatoid arthritis (RA), a chronic immune7ediated arthritis that affects up to 1% of the population2. Utilizing mass cytometry to detect activated T cells in RA synovial tissue revealed a strikingly expanded population of PD-1hi CXCR5- CD4+ T cells. These cells are not exhausted, Rather, multidimensional cytometry, transcriptomics, and functional assays define a population of PD-1hi CXCR5- ‘peripheral helper’ T (Tph) cells that express factors enabling B cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1hi CXCR5+ T ‘follicular helper’ (Tfh) cells, Tph cells induce plasma cell differentiation in vitro via IL-21 and SLAMF5-interactions3,4. However, global transcriptomics robustly separate Tph cells from Tfh cells, with altered expression of Bcl6 and Blimp-1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in Tph cells. Tph cells appear uniquely poised to promote B cell responses and antibody production within pathologically inflamed non-lymphoid tissues. |
| first_indexed | 2024-03-06T19:44:36Z |
| format | Journal article |
| id | oxford-uuid:21d6d92e-4159-4ab3-8674-bd0fefc22b76 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T19:44:36Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:21d6d92e-4159-4ab3-8674-bd0fefc22b762022-03-26T11:35:40ZPathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:21d6d92e-4159-4ab3-8674-bd0fefc22b76Symplectic Elements at OxfordNature Publishing Group2017Rao, DAGurish, MFMarshall, JLSlowikowski, KFonseka, CYLiu, YDonlin, LTHenderson, LAWei, KMizoguchi, FTeslovich, NCWeinblatt, MEMassarotti, EMCoblyn, JSHelfgott, SMLee, YCTodd, DJBykerk, VPGoodman, SMPernis, ABIvashkiv, LBKarlson, EWNigrovic, PAFiler, ABuckley, CDLederer, JARaychaudhuri, SBrenner, MBCD4+ T cells are central mediators of autoimmune pathology; however, the definition of their key effector functions in specific autoimmune diseases remains limited. Pathogenic CD4+ T cells within affected tissues may be identified by expression of markers of recent activation1. We applied this approach to joint tissue in rheumatoid arthritis (RA), a chronic immune7ediated arthritis that affects up to 1% of the population2. Utilizing mass cytometry to detect activated T cells in RA synovial tissue revealed a strikingly expanded population of PD-1hi CXCR5- CD4+ T cells. These cells are not exhausted, Rather, multidimensional cytometry, transcriptomics, and functional assays define a population of PD-1hi CXCR5- ‘peripheral helper’ T (Tph) cells that express factors enabling B cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1hi CXCR5+ T ‘follicular helper’ (Tfh) cells, Tph cells induce plasma cell differentiation in vitro via IL-21 and SLAMF5-interactions3,4. However, global transcriptomics robustly separate Tph cells from Tfh cells, with altered expression of Bcl6 and Blimp-1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in Tph cells. Tph cells appear uniquely poised to promote B cell responses and antibody production within pathologically inflamed non-lymphoid tissues. |
| spellingShingle | Rao, DA Gurish, MF Marshall, JL Slowikowski, K Fonseka, CY Liu, Y Donlin, LT Henderson, LA Wei, K Mizoguchi, F Teslovich, NC Weinblatt, ME Massarotti, EM Coblyn, JS Helfgott, SM Lee, YC Todd, DJ Bykerk, VP Goodman, SM Pernis, AB Ivashkiv, LB Karlson, EW Nigrovic, PA Filer, A Buckley, CD Lederer, JA Raychaudhuri, S Brenner, MB Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis |
| title | Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis |
| title_full | Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis |
| title_fullStr | Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis |
| title_full_unstemmed | Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis |
| title_short | Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis |
| title_sort | pathologically expanded peripheral t helper cell subset drives b cells in rheumatoid arthritis |
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