Decreased Frequencies of Peripheral Blood CD4+CD25+CD127–Foxp3+ in Patients with Graves’ Disease and Graves’ Orbitopathy: Enhancing Effect of Insulin Growth Factor-1 on Treg Cells

Przemyslaw Pawlowski; Kamil Grubczak; Jerzy Kostecki; Elzbieta Ilendo-Poskrobko; Marcin Moniuszko; Malgorzata Pawlowska; Robert Rejdak; Joanna Reszec; Janusz Mysliwiec

doi:10.1055/s-0042-122780

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2017; 49(03): 185-191
DOI: 10.1055/s-0042-122780

Endocrine Care

Decreased Frequencies of Peripheral Blood CD4⁺CD25⁺CD127^–Foxp3⁺ in Patients with Graves’ Disease and Graves’ Orbitopathy: Enhancing Effect of Insulin Growth Factor-1 on Treg Cells

Przemyslaw Pawlowski

¹Department of Medical Pathomorphology, Cathedral of Biostructure, Medical University of Bialystok, Bialystok, Poland

²Department of Paediatric Ophthalmology with Strabismus Treatment Unit, Medical University of Bialystok, Bialystok, Poland

³Department of Ophthalmology, Provincial Combined Hospital in Bialystok, Bialystok, Poland

,

Kamil Grubczak

⁴Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland

,

Jerzy Kostecki

⁵Department of Nuclear Medicine, Medical University of Bialystok, Bialystok, Bialystok, Poland

,

Elzbieta Ilendo-Poskrobko

⁶Department of Paediatric Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland

,

Marcin Moniuszko

⁴Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland

⁷Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland

,

Malgorzata Pawlowska

⁸Department of Haematology, Medical University of Bialystok, Bialystok, Poland

,

Robert Rejdak

⁹Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland

,

Joanna Reszec

¹Department of Medical Pathomorphology, Cathedral of Biostructure, Medical University of Bialystok, Bialystok, Poland

,

Janusz Mysliwiec

⁵Department of Nuclear Medicine, Medical University of Bialystok, Bialystok, Bialystok, Poland

› Author Affiliations

Abstract

Graves’ orbitopathy (GO) is characterized by orbital T cell infiltration. We evaluated the regulatory T (Treg) cell fractions induced with IGF-1 in Graves’ disease (GD) with and without GO. Peripheral blood mononuclear cells (PBMCs) were obtained from 13 patients with GD without eye manifestations; 10 patients with active GO; and 12 patients with nodular goiter (NG). All the patients from GD, GO, and NG were subclinical hyperthyroid. We analyzed the expression of Treg cell markers (CD4, CD25, CD127^–, Foxp3) on T cells and their ability to respond to IGF-1 stimulation. In patients with GD without GO, we found lowered percentages of CD4⁺ Foxp3⁺ cells, as compared to nodular goiter 1.77 vs. 5.42% (p=0.0276). Similarly, significantly reduced frequencies of CD4⁺CD25⁺CD127^–Foxp3⁺ and CD4⁺CD25⁺CD127^– cells were observed in GD patients as compared to nodular goiter patients with hyperthyreosis, (0.7 vs. 1.48%) (p=0.0071) and (14.5 vs. 37.2%) (p=0.0051), respectively. In GO with active GO, only the percentage of CD4⁺CD25⁺CD127^– cells was found to be decreased versus nodular goiter (9.35 vs. 37.2) (p=0.0275). Stimulation of PBMC derived from GO patients with IGF-1 resulted in significant increase of frequency of both CD4⁺ Foxp3⁺ and CD4⁺CD25⁺CD127^– Foxp3 cells. Decreased frequencies of peripheral blood CD4⁺CD25⁺CD127^–Foxp3⁺ in patients with GD and GO could be an useful marker of autoimmune process and perhaps a possible target for future therapies. This is the first study demonstrating Treg-enhancing effects of IGF-1. Thus IGF-1 can be accounted for modulating Treg cell-related action in GO.

Key words

tregs - IGF-1 stimulation - Graves’ orbitopathy - Foxp3 - CD127^– - autoimmunity

Full Text

References

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