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Helfgott, Simon

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Helfgott, Simon

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Author's Publications: search.filters.isAuthorOfPublication.917dac43-a59d-4c3a-b1a2-90cd301a4552

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    Pathologically Expanded Peripheral T Helper Cell Subset Drives B Cells in Rheumatoid Arthritis
    (Springer Science and Business Media LLC, 2017-02-02) Rao, Deepak; Gurish, Michael F.; Marshall, Jennifer L.; Slowikowski, Kamil; Fonseka, Chamith Y.; Liu, Yanyan; Donlin, Laura T.; Henderson, Lauren; Wei, Kevin; Mizoguchi, Fumitaka; Teslovich, Nikola; Weinblatt, Michael; Massarotti, Elena; Coblyn, Jonathan; Helfgott, Simon; Lee, Yvonne C.; Todd, Derrick; Bykerk, Vivian P.; Goodman, Susan M.; Pernis, Alessandra B.; Ivashkiv, Lionel B.; Karlson, Elizabeth; Nigrovic, Peter; Filer, Andrew; Buckley, Christopher D.; Lederer, James; Raychaudhuri, Soumya; Brenner, Michael
    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 activation1. Here, we used mass cytometry to evaluate activated T cells in joint tissue from patients with rheumatoid arthritis (RA), a chronic immune-mediated arthritis that affects up to 1% of the population2. This approach revealed a strikingly expanded population of PD-1hi CXCR5- CD4+ T cells in RA synovium. 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.