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Home / Equine Research Bank / Sci Rep / Th1 and Th2 cells in equine endometrosis and their interacti...
Scientific reports2025; 15(1); 36263; doi: 10.1038/s41598-025-20152-0

Th1 and Th2 cells in equine endometrosis and their interactions with endometrial fibroblasts.

Abstract: Mare endometrosis is a chronic degenerative condition of the endometrium, primarily characterized by fibrosis, involving interactions among fibroblasts, immune cells, and epithelial cells regulated by cytokines and growth factors. T helper (Th)1 and Th2 cells seem to play a pivotal role in fibrosis. However, their roles in equine endometrial fibrosis remain unknown. This study explores Th1 and Th2 cell distribution across different stages of endometrium histopathological Kenney and Doig categories; and evaluated their secretome effects on non-fibrotic endometrium derived fibroblast functional characteristics, extracellular matrix (ECM)-associated mRNA transcription, and transcriptomic profiles. Th1 and Th2 cells, along with cytokines (IFN-γ, IL-4, IL-13) and their receptors, were present in mare endometria at all endometrium stages. Th1 secretome influenced genes enriched in metabolism, cell cycle, and ECM-related pathways, while Th2 secretome regulated genes enriched in tissue remodeling and signaling pathways, suggesting their role in the development of fibrosis in the endometrosis progression.
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Publication Date: 2025-10-16 PubMed ID: 41102323PubMed Central: PMC12533255DOI: 10.1038/s41598-025-20152-0Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigates the role of T helper (Th)1 and Th2 immune cells in the development of fibrosis in mare endometrium, a condition known as endometrosis.
  • It examines how these immune cells and their secreted factors interact with endometrial fibroblasts and contribute to fibrotic tissue changes at various stages of the disease.

Background

  • Mare endometrosis is a chronic, degenerative condition characterized by fibrosis (formation of excess fibrous connective tissue) in the endometrium, which negatively affects fertility in horses.
  • Fibrosis involves complex interactions among different cell types, including fibroblasts (cells that produce extracellular matrix), immune cells, and epithelial cells, regulated by cytokines (signaling proteins) and growth factors.
  • T helper cells (Th1 and Th2 subsets) play critical roles in immune responses and have been implicated in fibrosis development in various tissues, but their specific roles in equine endometrosis were previously unknown.

Objectives of the Study

  • To determine the distribution of Th1 and Th2 cells in mare endometria at different stages of fibrosis according to the Kenney and Doig histopathological classification.
  • To assess the effects of secreted factors (secretome) from Th1 and Th2 cells on the function of fibroblasts derived from non-fibrotic equine endometrium.
  • To examine how these secreted factors influence extracellular matrix (ECM)-related gene expression and broader transcriptomic changes in fibroblasts associated with fibrosis development.

Key Methods

  • Histopathological analysis of mare endometrial tissue samples categorized by the Kenney and Doig system to identify fibrosis stages and immune cell presence.
  • Identification and measurement of Th1 and Th2 cells and associated cytokines (IFN-γ for Th1; IL-4, IL-13 for Th2) and their receptors in the tissues.
  • In vitro experiments exposing non-fibrotic endometrial fibroblasts to secretomes from Th1 and Th2 cells.
  • Analysis of gene expression changes related to ECM production, cell cycle, metabolism, tissue remodeling, and intracellular signaling pathways using mRNA measurements and transcriptomic profiling.

Main Findings

  • Both Th1 and Th2 cells, along with their characteristic cytokines and receptors, were consistently present at all stages of the mare endometrium, regardless of fibrosis severity.
  • The secretome from Th1 cells influenced fibroblast gene expression mainly in pathways related to metabolism, cell cycle regulation, and the extracellular matrix, indicating a role in cellular proliferation and matrix remodeling processes.
  • The secretome from Th2 cells modulated genes associated with tissue remodeling and signaling pathways, suggesting their involvement in the structural changes and communication networks driving fibrosis progression.
  • The differential gene regulation by Th1 and Th2 cytokines implies a complex balance where these immune cells contribute distinctly to the development and progression of fibrotic lesions in endometrosis.

Conclusions and Implications

  • This study provides novel insights into how immune components, specifically Th1 and Th2 cells, contribute to the pathogenesis of equine endometrosis through direct interactions with endometrial fibroblasts.
  • Understanding the distinct roles of Th1 and Th2 secreted factors on fibroblast behavior and ECM production helps elucidate mechanisms of fibrotic tissue remodeling in the endometrium.
  • These findings could guide future therapeutic strategies targeting immune modulation to prevent or mitigate fibrosis in mare reproductive health, potentially improving fertility outcomes.

Cite This Article

APA
Wójtowicz A, Sadowska A, Molcan T, Słyszewska M, Drzewiecka EM, Tobolski D, Ferreira-Dias G, Szóstek-Mioduchowska A. (2025). Th1 and Th2 cells in equine endometrosis and their interactions with endometrial fibroblasts. Sci Rep, 15(1), 36263. https://doi.org/10.1038/s41598-025-20152-0

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 36263
PII: 36263

Researcher Affiliations

Wójtowicz, Anna
  • Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
Sadowska, Agnieszka
  • Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
Molcan, Tomasz
  • Molecular Biology Laboratory, Polish Academy of Sciences, Institute of Animal Reproduction and Food Research, Tuwima 10, 10-748, Olsztyn, Poland.
Słyszewska, Magda
  • Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
Drzewiecka, Ewa Monika
  • Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
Tobolski, Dawid
  • Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787, Warsaw, Poland.
Ferreira-Dias, Graça
  • Faculty of Veterinary Medicine, CIISA-Center for Interdisciplinary Research in Animal Health, University of Lisbon, Lisbon, Portugal.
  • Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Lisbon, Portugal.
Szóstek-Mioduchowska, Anna
  • Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland. a.szostek-mioduchowska@pan.olsztyn.pl.

MeSH Terms

  • Animals
  • Horses
  • Female
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Fibroblasts / metabolism
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Endometrium / pathology
  • Endometrium / metabolism
  • Endometrium / immunology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Horse Diseases / immunology
  • Horse Diseases / pathology
  • Horse Diseases / metabolism
  • Endometriosis / veterinary
  • Endometriosis / immunology
  • Endometriosis / pathology
  • Endometriosis / metabolism
  • Cytokines / metabolism
  • Fibrosis
  • Transcriptome
  • Extracellular Matrix / metabolism

Grant Funding

  • 2019/35/D/NZ9/02989 / Narodowym Centrum Nauki
  • 2019/35/D/NZ9/02989 / Narodowym Centrum Nauki
  • 2019/35/D/NZ9/02989 / Narodowym Centrum Nauki
  • 2019/35/D/NZ9/02989 / Narodowym Centrum Nauki

Conflict of Interest Statement

Declarations. Competing interests: The authors declare no competing interests.

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