Regulatory T Cell Sub-Populations in Patients with Distinct Autoimmune/Inflammatory Diseases With or Without Inborn Errors of Immunity
<b>Background</b>: Regulatory T cells (Tregs) are the main suppressor cells that maintain immune tolerance and prevent autoimmunity. Changes in Treg number or function are implicated in a wide range of autoimmune and inflammatory (AI/I) diseases, with or without underlying inborn errors...
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2025-07-01
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| author | Sevil Oskay Halacli Dilan Inan Saliha Esenboga Hacer Neslihan Bildik Aslihan Berra Bolat Ilhan Tezcan Deniz Cagdas |
| author_facet | Sevil Oskay Halacli Dilan Inan Saliha Esenboga Hacer Neslihan Bildik Aslihan Berra Bolat Ilhan Tezcan Deniz Cagdas |
| author_sort | Sevil Oskay Halacli |
| collection | DOAJ |
| description | <b>Background</b>: Regulatory T cells (Tregs) are the main suppressor cells that maintain immune tolerance and prevent autoimmunity. Changes in Treg number or function are implicated in a wide range of autoimmune and inflammatory (AI/I) diseases, with or without underlying inborn errors of immunity (IEI). Understanding the phenotypic profiles of Treg subsets and their associations with immune dysregulation is crucial to identifying potential robust and holistic biomarkers for disease activity. <b>Methods</b>: We examined peripheral blood mononuclear cells from 40 patients diagnosed with various autoimmune/inflammatory diseases, including those with genetically confirmed inborn errors of immunity (IEIs), and compared these samples to those from 38 healthy controls of the same age. Utilizing multiparametric flow cytometry, we measured multiple Treg sub-populations and investigated their correlations with lymphocyte subset profiles and the diversity of autoantibodies. We applied advanced statistical and machine learning techniques, such as t-SNE, k-means clustering, and ROC analysis, to analyze immunophenotypic patterns in the patients. <b>Results</b>: Among all Treg sub-populations, only CD4<sup>+</sup>CD127<sup>low</sup>CD25<sup>high</sup>FOXP3<sup>+</sup> Tregs showed a significant decrease in patients compared to healthy controls (<i>p</i> < 0.05), while other Treg phenotypes did not differ. FOXP3 expression showed reduced intensity in patients and demonstrated diagnostic potential (AUC = 0.754). Notably, this Treg subset negatively correlated with CD19<sup>+</sup> B cell percentages and positively correlated with the diversity of circulating autoantibodies. Unsupervised clustering revealed three distinct immunophenotypic profiles, highlighting heterogeneity among patients and underlining FOXP3-centered immune dysregulation. <b>Conclusions</b>: Our results presented that patients have an impairment in the CD4<sup>+</sup>CD127<sup>low</sup>CD25<sup>high</sup>FOXP3<sup>+</sup> regulatory T cell subset, which is identified by significantly decreased frequency and decreased expression of FOXP3. Immunological heterogeneity among patients was further uncovered by unsupervised clustering, highlighting the critical role that FOXP3-centered regulatory failure plays in the pathophysiology of illness. The combined evaluation of these three immunological factors, centered around FOXP3, holds promise as an integrative tool for monitoring disease progression across various autoimmune and immunodeficient contexts. |
| format | Article |
| id | doaj-art-ca766c0e09334ff59f09bdd2a0353da4 |
| institution | Kabale University |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj-art-ca766c0e09334ff59f09bdd2a0353da42025-08-20T04:00:49ZengMDPI AGDiagnostics2075-44182025-07-011515187910.3390/diagnostics15151879Regulatory T Cell Sub-Populations in Patients with Distinct Autoimmune/Inflammatory Diseases With or Without Inborn Errors of ImmunitySevil Oskay Halacli0Dilan Inan1Saliha Esenboga2Hacer Neslihan Bildik3Aslihan Berra Bolat4Ilhan Tezcan5Deniz Cagdas6Division of Pediatric Immunology, Department of Basic Sciences of Pediatrics, Institute of Child’s Health, Ankara 06230, TurkeyDivision of Pediatric Immunology, Department of Basic Sciences of Pediatrics, Institute of Child’s Health, Ankara 06230, TurkeyDivision of Pediatric Immunology, Department of Basic Sciences of Pediatrics, Institute of Child’s Health, Ankara 06230, TurkeyDivision of Pediatric Immunology, Department of Basic Sciences of Pediatrics, Institute of Child’s Health, Ankara 06230, TurkeyFaculty of Medicine, Hacettepe University, Ankara 06100, TurkeyDivision of Pediatric Immunology, Department of Basic Sciences of Pediatrics, Institute of Child’s Health, Ankara 06230, TurkeyDivision of Pediatric Immunology, Department of Basic Sciences of Pediatrics, Institute of Child’s Health, Ankara 06230, Turkey<b>Background</b>: Regulatory T cells (Tregs) are the main suppressor cells that maintain immune tolerance and prevent autoimmunity. Changes in Treg number or function are implicated in a wide range of autoimmune and inflammatory (AI/I) diseases, with or without underlying inborn errors of immunity (IEI). Understanding the phenotypic profiles of Treg subsets and their associations with immune dysregulation is crucial to identifying potential robust and holistic biomarkers for disease activity. <b>Methods</b>: We examined peripheral blood mononuclear cells from 40 patients diagnosed with various autoimmune/inflammatory diseases, including those with genetically confirmed inborn errors of immunity (IEIs), and compared these samples to those from 38 healthy controls of the same age. Utilizing multiparametric flow cytometry, we measured multiple Treg sub-populations and investigated their correlations with lymphocyte subset profiles and the diversity of autoantibodies. We applied advanced statistical and machine learning techniques, such as t-SNE, k-means clustering, and ROC analysis, to analyze immunophenotypic patterns in the patients. <b>Results</b>: Among all Treg sub-populations, only CD4<sup>+</sup>CD127<sup>low</sup>CD25<sup>high</sup>FOXP3<sup>+</sup> Tregs showed a significant decrease in patients compared to healthy controls (<i>p</i> < 0.05), while other Treg phenotypes did not differ. FOXP3 expression showed reduced intensity in patients and demonstrated diagnostic potential (AUC = 0.754). Notably, this Treg subset negatively correlated with CD19<sup>+</sup> B cell percentages and positively correlated with the diversity of circulating autoantibodies. Unsupervised clustering revealed three distinct immunophenotypic profiles, highlighting heterogeneity among patients and underlining FOXP3-centered immune dysregulation. <b>Conclusions</b>: Our results presented that patients have an impairment in the CD4<sup>+</sup>CD127<sup>low</sup>CD25<sup>high</sup>FOXP3<sup>+</sup> regulatory T cell subset, which is identified by significantly decreased frequency and decreased expression of FOXP3. Immunological heterogeneity among patients was further uncovered by unsupervised clustering, highlighting the critical role that FOXP3-centered regulatory failure plays in the pathophysiology of illness. The combined evaluation of these three immunological factors, centered around FOXP3, holds promise as an integrative tool for monitoring disease progression across various autoimmune and immunodeficient contexts.https://www.mdpi.com/2075-4418/15/15/1879regulatory T cellssub-populationautoimmune diseaseinflammatory diseaseprimary immunodeficiency |
| spellingShingle | Sevil Oskay Halacli Dilan Inan Saliha Esenboga Hacer Neslihan Bildik Aslihan Berra Bolat Ilhan Tezcan Deniz Cagdas Regulatory T Cell Sub-Populations in Patients with Distinct Autoimmune/Inflammatory Diseases With or Without Inborn Errors of Immunity Diagnostics regulatory T cells sub-population autoimmune disease inflammatory disease primary immunodeficiency |
| title | Regulatory T Cell Sub-Populations in Patients with Distinct Autoimmune/Inflammatory Diseases With or Without Inborn Errors of Immunity |
| title_full | Regulatory T Cell Sub-Populations in Patients with Distinct Autoimmune/Inflammatory Diseases With or Without Inborn Errors of Immunity |
| title_fullStr | Regulatory T Cell Sub-Populations in Patients with Distinct Autoimmune/Inflammatory Diseases With or Without Inborn Errors of Immunity |
| title_full_unstemmed | Regulatory T Cell Sub-Populations in Patients with Distinct Autoimmune/Inflammatory Diseases With or Without Inborn Errors of Immunity |
| title_short | Regulatory T Cell Sub-Populations in Patients with Distinct Autoimmune/Inflammatory Diseases With or Without Inborn Errors of Immunity |
| title_sort | regulatory t cell sub populations in patients with distinct autoimmune inflammatory diseases with or without inborn errors of immunity |
| topic | regulatory T cells sub-population autoimmune disease inflammatory disease primary immunodeficiency |
| url | https://www.mdpi.com/2075-4418/15/15/1879 |
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