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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
Elżbieta  SupruniukElżbieta Supruniuk1*Kamil  GrubczakKamil Grubczak1Anna  Parfieniuk-KowerdaAnna Parfieniuk-Kowerda1Robert  FlisiakRobert Flisiak1Marcin  MoniuszkoMarcin Moniuszko1Jerzy  JaroszewiczJerzy Jaroszewicz2Adrian  ChabowskiAdrian Chabowski1Magdalena  ŚwiderskaMagdalena Świderska3
  • 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

The final, formatted version of the article will be published soon.

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

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