Effect of Interferon alfa-2a Treatment on Adaptive and Innate Immune Systems in Patients With Behçet Disease Uveitis

Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):52-63. doi: 10.1167/iovs.18-25548.

Abstract

Purpose: To investigate the effect of interferon alfa-2a on T regulatory (Treg) cells, T helper 17 (Th17) cells, and expression of Toll-like receptors (TLRs) in Behçet disease (BD) patients with uveitis.

Methods: Twenty-seven patients who received interferon alfa-2a for active BD uveitis despite conventional immunomodulatory therapies and healthy controls were enrolled. Peripheral blood Treg and Th17 cell frequencies were determined by flow cytometry as gated cells for CD3+CD4+Foxp3+ and CD3+CD4+IL17A+, respectively. Th17 RAR-related orphan receptor (ROR)γt mRNA expression was verified by real-time PCR (RT-PCR). Treg and Th17 cell cytokines were detected by ELISA in the supernatant of short-term cell cultures. RT-PCR was used to assess expression of TLR-2, TLR-3, TLR-4, TLR-8, and TLR-9 using cDNA prepared from CD4+ T cells and monocytes.

Results: Treg and Th17 cell frequencies and Th17 RORγt expression were significantly elevated, and IL-10 concentration in Treg cell supernatants was significantly lower in BD patients than in controls. Th17 IL-17, IL-6, IL-21, IL-22, IL-23, IFN-γ, and TNF-α concentrations were significantly higher and all TLR expressions were significantly elevated in patients. Interferon alfa-2a led to a significant reversal in Treg and Th17 cell frequencies, Th17 RORγt expression, Treg and Th17 cell cytokine production, and TLR expression by CD4+ T cells and monocytes.

Conclusions: Despite a relative increase in Treg cells, impaired IL-10 production suggests that Treg dysfunction may play a role in induction of BD uveitis. Favorable effects of interferon alfa-2a may be associated with recovery of Treg cell function, suppression of Th17 cells, and reduced expression of TLRs on CD4+ T cells and monocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology*
  • Adolescent
  • Adult
  • Antiviral Agents / therapeutic use*
  • Behcet Syndrome / diagnosis
  • Behcet Syndrome / drug therapy*
  • Behcet Syndrome / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cross-Sectional Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Fluorescein Angiography
  • Humans
  • Immunity, Innate / immunology*
  • Interferon alpha-2 / therapeutic use*
  • Male
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Prospective Studies
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / immunology
  • Toll-Like Receptors / metabolism
  • Uveitis / diagnosis
  • Uveitis / drug therapy*
  • Uveitis / immunology
  • Young Adult

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Messenger
  • Toll-Like Receptors