loading page

Impaired function of PD-1+ follicular regulatory T cells in systemic lupus erythematosus
  • +5
  • Izumi Kurata,
  • Natsuko Mikami,
  • Ayako Ohyama,
  • Atsumu Osada,
  • Yuya Kondo,
  • Hiroto Tsuboi,
  • T Sumida,
  • Isao Matsumoto
Izumi Kurata
Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
Author Profile
Natsuko Mikami
Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba
Author Profile
Ayako Ohyama
University of Tsukuba Faculty of Medicine
Author Profile
Atsumu Osada
University of Tsukuba Faculty of Medicine
Author Profile
Yuya Kondo
University of Tsukuba
Author Profile
Hiroto Tsuboi
University of Tsukuba
Author Profile
T Sumida
University of Tsukuba
Author Profile
Isao Matsumoto
University of Tsukuba
Author Profile

Abstract

Aberrant autoantibody production is characteristic of systemic lupus erythematosus (SLE), but follicular regulatory T (TFR) cells potentially can suppress this abnormality. We investigate functional changes in TFR cells from SLE patients. Circulating TFR cells were collected from 19 SLE patients and 14 healthy controls (HC) to compare molecular expression and in vitro suppressive capacity of follicular helper T (TFH) cell proliferation. To reveal the stability of Foxp3 in TFR, pyrosequencing of conserved non-coding sequence (CNS) 2 at the Foxp3 gene locus was performed. We then tested IL-2 in SLE-TFR cells to check restoration of suppressor function. Programmed death-1 (PD-1) expression in SLE-TFR cells was positively correlated with anti-DNA antibody levels and disease activity. These cells had impaired suppressive function for TFH cells with decreased expression of suppression mediators forkhead box p3 (Foxp3), cytotoxic T-lymphocyte antigen 4 (CTLA4), and IL-2 receptor alpha (IL2Rα). Pyrosequencing identified hyper-methylation in CNS2 region of SLE-TFR cells comparing to HC. With In vitro IL-2 stimulation, PD-1 expression of TFR cells significantly decreased along with increased expression of Foxp3 and CTLA-4, especially in low-dose. Thus, SLE-TFR cells have functionally defective to TFH suppression, but low-dose IL-2 therapy might be useful to restore this ability.

Peer review status:UNDER REVIEW

04 Jun 2021Submitted to Clinical & Experimental Immunology
04 Jun 2021Assigned to Editor
04 Jun 2021Submission Checks Completed
07 Jun 2021Reviewer(s) Assigned