Analysis of LAP+ and GARP+ Treg subsets in peripheral blood of patients with neuromyelitis optica spectrum disorders

Neurol Sci. 2023 May;44(5):1739-1747. doi: 10.1007/s10072-023-06629-8. Epub 2023 Jan 23.

Abstract

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a group of antibody-mediated inflammatory demyelinating central nervous system diseases. T lymphocytes participate in NMOSD pathogenesis, with regulatory T cells (Treg) being the core in maintaining immune homeostasis. Studies have revealed that different Treg subsets play different roles in autoimmune diseases. The distribution of LAP+ or GARP+ Treg subsets in NMOSD may help us deeply understand their immune mechanism.

Methods: This study reviewed 22 NMOSD patients and 20 normal controls. Flow cytometric analysis was utilized to detect subsets of Treg cells expressing Foxp3, Helios, LAP, or GARP in peripheral blood. ELISA was used to detect plasma TGF-β1 and IL-10. In addition, changes in the proportion of Treg cell subsets before and after glucocorticoid treatment in 10 patients were analyzed.

Results: Compared with healthy controls, LAP and GARP expressions were significantly downregulated in the peripheral blood of NMOSD patients. TGF-β1 expression in NMOSD patients was lower and was positively correlated with the ratio of CD4+GARP+ Treg cells. After treatment with glucocorticoid, LAP and GARP expressions in the peripheral blood of NMOSD patients were upregulated.

Conclusions: The proportion of Treg cells expressing LAP and GARP is downregulated, implying that Treg cells with the best inhibitory function are insufficient to maintain autoimmune homeostasis in NMOSD patients. Upregulation of Treg cells expressing LAP and GARP in NMOSD patients may be one of the mechanisms of glucocorticoid treatment.

Keywords: Glycoprotein A repetitions predominant; Latency-associated peptide; Neuromyelitis optica spectrum disorders; Regulatory T cells; Transforming growth factor-β1.

MeSH terms

  • Glucocorticoids / therapeutic use
  • Humans
  • Membrane Proteins* / immunology
  • Neuromyelitis Optica* / drug therapy
  • Neuromyelitis Optica* / immunology
  • T-Lymphocytes, Regulatory* / immunology
  • Transforming Growth Factor beta1* / immunology

Substances

  • Glucocorticoids
  • LRRC32 protein, human
  • Membrane Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta1