--- - |2 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. - Journal of Cellular Physiology, Volume 233, Issue 11, Page 8767-8777, November 2018.