The Imbalance of Circulating T Helper Subsets and Regulatory T Cells in Patients With Lrba Deficiency: Correlation With Disease Severity Publisher Pubmed



Azizi G^{1, 2, 3} ; Mirshafiey A^{2, 4} ; Abolhassani H^{2, 3, 5} ; Yazdani R² ; Ghanavatinejad A⁴ ; Noorbakhsh F⁶ ; Rezaei N^{2, 3, 6} ; Aghamohammadi A²
Source: Journal of Cellular Physiology Published:2018

Abstract

Patients with lipopolysaccharides responsive beige-like anchor protein (LRBA) deficiency suffer from a variety of immunological abnormalities. In the current study, we investigated the role of T helper (Th) cell subsets and regulatory T (Treg) cells and their related cytokines and transcription factors in the immune dysregulation of LRBA deficiency. The study population comprised of 13 LRBA-deficient patients and 13 age- and sex-matched healthy controls (HCs). Th subsets and Treg were examined by flow cytometry. The expression of determinant cytokines (interferon-γ [IFN-γ], interleukin [IL]-17, IL-22, and IL-10), and cell subset–specific transcription factors were evaluated before and after proliferation and activation stimuli. The frequencies of Th1, Th1-like Th17 and Th22 cells along with the expression of T-box transcription factor (TBET) and runt-related transcription factor 1 (RUNX1) were significantly increased in patients with LRBA. Moreover, IFN-γ and IL-22 production in LRBA-deficient CD4+ T cells were elevated after lymphocyte stimulation, particularly in patients with enteropathy. However, CD4+CD25+FoxP3+CD127− cells were significantly decreased in LRBA-deficient patients compared with those of HCs, particularly in patients with autoimmunity. There was a negative correlation between the frequencies of CD4+CD25+FoxP3+CD127− cells and Th1-like Th17 cells in LRBA-deficient patients, and an overlapping phenotype of autoimmunity and enteropathy were observed in ~70% of patients. The frequency of Th17 cells was lower in patients with enteropathy, while Th1-like Th17 cells were higher than in those without enteropathy. Our findings demonstrated an imbalance in Th subsets, mainly in Th1-like Th17 and Treg cells and their corresponding cytokines in LRBA deficiency, which might be important in the immunopathogenesis of autoimmunity and enteropathy. © 2018 Wiley Periodicals, Inc.