title: Inhibition of aberrant circulating Tfh cell proportions by corticosteroids in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  To observe the proportion of peripheral T follicular helper (Tfh) cells in patients with systemic lupus erythematosus (SLE) and to assess the role of steroids on Tfh cells from SLE patients.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) from 42 SLE patients and 22 matched healthy subjects were collected to assess proportions of circulating CXCR5(+)PD1(+)/CD4(+) T cells (Tfh), CD4(+)CCR6(+) T cells (Th17-like) and CD19(+)CD138(+) plasma cells by flow cytometry. 8 of the patients had their blood redrawn within one week after receiving methylprednisolone pulse treatment. Disease activity was evaluated by SLE disease activity index. To test the effect of IL-21 and corticosteroids on Tfh cells in vitro, PBMCs harvested from another 15 SLE patients were cultured with medium, IL-21, or IL-21+ dexamethasone for 24 hours and 72 hours. PBMCs from an independent 23 SLE patients were cultured with different concentrations of dexamethasone for 24 hours.
  
  
  RESULTS
  Compared to normal controls, percentages of circulating Tfh cells, but not Th17 cells, were elevated in SLE patients and correlated with disease activity. Proportions of Tfh cells in SLE patients were positively correlated with those of plasma cells and serum levels of antinuclear antibodies. After methylprednisolone pulse treatment, both percentages and absolute numbers of circulating Tfh cells were significantly decreased. In vitro cultures showed an increase of Tfh cell proportion after IL-21 stimulation that was totally abolished by the addition of dexamethasone. Both 0.5 and 1 µM dexamethasone decreased Tfh cells dose dependently (overall p = 0.013).
  
  
  CONCLUSIONS
  We demonstrated that elevated circulating Tfh cell proportions in SLE patients correlated with their disease activities, and circulating levels of plasma cells and ANA. Corticosteroids treatment down-regulated aberrant circulating Tfh cell proportions both in vivo and in vitro, making Tfh cells a new treatment target for SLE patients.
authors.affiliation: Department of Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Feng
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Bingzhu
authors.initials: B
authors.lastname: Hua
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007378:Interleukins / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000378:metabolism; D053668:Syndecan-1 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D000305:Adrenal Cortex Hormones; D018941:Antigens, CD19; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D007378:Interleukins; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5; D053668:Syndecan-1; D000098546:Interleukin-21