title: Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity.
abstract: Regulatory T cells were investigated in early-onset (EO) and late-onset (LO) myasthenia gravis patients with anti-acetylcholine receptor antibody (AChR-MG). Alterations in PD-1 and PD-L1 on CD4(+)CD25(++) (Treg) and responder T cells (Tresp, CD4(+)CD25(-)) were observed in LOMG patients. GITR was decreased on CD4(+)CD25(++) of all patients. Decrease of FOXP3 was associated with lower phosphorylation of STAT5.1,25-dihydroxyvitamin D3 (VitD3) increased suppression in co-culture with a stronger effect in patients by acting possibly both on cell groups. Changes in surface molecules and intracellular pathways contribute to the defects of Treg in non-thymomatous AChR-MG and VitD3 can have modulatory effects.
authors: Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey; Department of Immunology, Institute of Experimental Medicine (DETAE), Istanbul University, Istanbul, Turkey.
authors: Mahdi
authors: M
authors: Alahgholi-Hajibehzad
authors: Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors: Piraye
authors: P
authors: Oflazer
authors: Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.
authors: Fikret
authors: F
authors: Aysal
authors: Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors: Hacer
authors: H
authors: Durmuş
authors: Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors: Yeşim
authors: Y
authors: Gülşen-Parman
authors: Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Alexander
authors: A
authors: Marx
authors: Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors: Feza
authors: F
authors: Deymeer
authors: Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey. Electronic address: gsaruhan@istanbul.edu.tr.
authors: Güher
authors: G
authors: Saruhan-Direskeneli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000378:metabolism*; D010641:Phenotype; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D050799:STAT5 Transcription Factor; D002117:Calcitriol
keywords: GITR; LOMG; PD-1; STAT-5; Treg; Vitamin D