ORIGINAL RESEARCH article
Front. Immunol.
Sec. T Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1597204
Increased frequencies of human Th-17 CD4+ T-cells and decreased Tregulatory cells in patients with early and advanced metabolic dysfunction-associated steatotic liver disease (MASLD)
Provisionally accepted- 1Medical University of Bialystok, Bialystok, Poland
- 2Department of Infectious Diseases and Hepatology, Medical University of Silesia, Bytom, Poland
- 3Medical Diagnostic and Microbiological Laboratory of Ludwik Rydygier Hospital, Suwałki, Poland
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Dysregulation of immune responses may influence the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH). Our recent data suggest the role of Th17-related cytokines in fibrosis advancement in MASLD. Herein, we aimed to analyze T-regulatory and Th17-producing Tlymphocytes by flow cytometry with respect to MASLD progression. Methods: Extensive immunophenotyping was performed in a subset of 30 patients with MASLD diagnosed by elastography and ultrasonography and 15 healthy controls (HCs). Ex-vivo surface (CD4, CD25, CD127) and intracellular cytokine expressions (IL-10, IL-17, Foxp3, RORgt) were analyzed by flow cytometry (BD FACS-Calibur). Plasma concentrations of selected interleukins such as IL-10, IL22, and IL-17A were measured by ELISA. Results: 19/30 (63%) of MASLD patients were diagnosed with steatosis with inflammation (advanced MASLD) as compared to simple steatosis (early MASLD) using elastography. The percentage of IL-17-producing cells among CD4(+) T-lymphocytes was two-fold more frequent (1.70% vs. 0.73%), while of T-regulatory cells (CD4+CD25+Foxp3+, T-regs) lower (3.57% vs. 6.56%) in advanced MASLD compared to HCs. This resulted in an aberrated ratio of Th17 to Tregs in MASLD (p=0.004). The frequency of T-regulatory cells (CD4+CD25+Foxp3+, Tregs) declined also in the advanced MASLD patients (3.57%) compared to the early stage disease (5.16%). Importantly, IL-10 and IL-17A serum levels positively correlated with CD4+IL-17+/CD4+CD25+Foxp3+ ratio. Plasma IL-10/IL-17A ratio and IL-10/IL-22 ratio significantly differed between F0 fibrosis vs. moderate (F2). Conclusions: The imbalance between Th17 and T-regulatory immune responses is present not only at cytokine level but also at a cellular level in MASLD. Especially in advanced disease, a higher percentage of IL-17 producing T-cells is coupled with the lower number of T-regulatory cells.
Keywords: MASLD, Th17 CD4+ T-cells, T-regulatory cells, Fibrosis, IL-10, IL-17A, IL-22
Received: 21 Mar 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Supruniuk, Grubczak, Parfieniuk-Kowerda, Flisiak, Moniuszko, Jaroszewicz, Chabowski and Świderska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Elżbieta Supruniuk, Medical University of Bialystok, Bialystok, Poland
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.