@article{94ad7133e29648ea97a7a8d8b51cb0b5,
title = "PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21",
abstract = "Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathologic T cell-B cell interactions and autoantibody production. Defining the T cell populations that drive B cell responses in SLE may enable design of therapies that specifically target pathologic cell subsets. Here, we evaluated the phenotypes of CD4+ T cells in the circulation of 52 SLE patients drawn from multiple cohorts and identified a highly expanded PD-1hiCXCR5-CD4+ T cell population. Cytometric, transcriptomic, and functional assays demonstrated that PD-1hiCXCR5-CD4+ T cells from SLE patients are T peripheral helper (Tph) cells, a CXCR5- T cell population that stimulates B cell responses via IL-21. The frequency of Tph cells, but not T follicular helper (Tfh) cells, correlated with both clinical disease activity and the frequency of CD11c+ B cells in SLE patients. PD-1hiCD4+ T cells were found within lupus nephritis kidneys and correlated with B cell numbers in the kidney. Both IL-21 neutralization and CRISPR-mediated deletion of MAF abrogated the ability of Tph cells to induce memory B cell differentiation into plasmablasts in vitro. These findings identify Tph cells as a highly expanded T cell population in SLE and suggest a key role for Tph cells in stimulating pathologic B cell responses.",
author = "Bocharnikov, {Alexandra V.} and Joshua Keegan and Wacleche, {Vanessa S.} and Ye Cao and Fonseka, {Chamith Y.} and Guoxing Wang and Muise, {Eric S.} and Zhang, {Kelvin X.} and Arnon Arazi and Gregory Keras and Li, {Zhihan J.} and Yujie Qu and Gurish, {Michael F.} and Michelle Petri and Buyon, {Jill P.} and Chaim Putterman and David Wofsy and James, {Judith A.} and Guthridge, {Joel M.} and Betty Diamond and Anolik, {Jennifer H.} and Mackey, {Matthew F.} and Alves, {Stephen E.} and Nigrovic, {Peter A.} and Costenbader, {Karen H.} and Brenner, {Michael B.} and Lederer, {James A.} and Rao, {Deepak A.}",
note = "Funding Information: This work was supported, in part, by funding from the Lupus Research Alliance, Rheumatology Research Foundation, Tobe and Stephen E. Malawista, MD Endowment in Academic Rheumatology, Burroughs Wellcome Fund Career Award in Medical Sciences, and NIAMS K08 AR072791 to DAR. AVB was supported by a Rheumatology Research Foundation and Medical Graduate Student Preceptorship. AVB and PAN were supported by the Fundaci{\'o}n Bechara, and PAN was supported by funding from the Lupus Research Alliance, NIAMS P30 AR070253, and NIAMS R01 AR065538. We thank Adam Chicoine and the BWH Human Immunology Center Flow Cytometry Core for cell sorting assistance. We thank Jason Gilliland, Sophia Zara-khovich, and Kimberly Kerr from Merck & Co. Inc. for their assistance in RNA-seq data processing. Publisher Copyright: {\textcopyright} 2019 American Society for Clinical Investigation. All rights reserved.",
year = "2019",
month = sep,
day = "19",
doi = "10.1172/jci.insight.130062",
language = "English (US)",
volume = "4",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "20",
}