# The TPx protein of Taenia solium metacestode regulates Treg and Th17 cell differentiation via the TGF-β/Smad signaling pathway

## TL;DR

This study shows how a protein from a tapeworm affects immune cells, causing an imbalance that could help explain how a parasitic infection causes disease.

## Contribution

The study identifies the TGF-β/Smad pathway as a novel mechanism by which TPx protein regulates Treg and Th17 cell differentiation.

## Key findings

- TPx protein induces a Treg/Th17 cell imbalance through TGF-β/Smad signaling.
- Foxp3 expression increases while RORC(γt) decreases in TPx-treated cells.
- TGF-β1, TGF-βR2, and p-Smad3 are upregulated following TPx exposure.

## Abstract

The immunopathogenesis of cysticercosis remains elusive. This study investigates the effects of Taenia solium metacestode-derived thioredoxin peroxidase (TPx) protein on regulatory T (Treg) cells and T helper 17 (Th17) cell differentiation, as well as its correlation with signaling pathways in human Jurkat T lymphocytes exposed to TPx for varying durations, to provide a scientific basis for further studying the immune pathogenesis and clinical treatment of cysticercosis.

TPx protein from the excretory-secretory antigens of T. solium metacestode was used to stimulate Jurkat cells at various timepoints. Flow cytometry was employed to detect the expression of CD4+CD25+CD127- Treg cells and CD4+IL-17A+ Th17 cells. Transcriptomic analysis was performed to identify the signaling pathways related to the differentiation of Jurkat cells under the influence of the TPx protein at different time points. The expression levels of TGF-β1, TGF-βR2, Smad4, Foxp3, RORC(γt), and phosphorylated Smad3 proteins were measured in TPx-treated cells and control cells at different time points.

A Treg/Th17 cell imbalance was detected in Jurkat cells following exposure to TPx, characterized by a Treg-mediated predominant immunosuppressive response. Gene Set Enrichment Analysis identified significant enrichment of the TGF-β signaling pathway and Th17 cell differentiation pathway in TPx-treated cells. TPx significantly upregulated TGF-β1, TGF-βR2, and p-Smad3 expression in cells (P < 0.05). Concurrently, the expression of Foxp3, a key transcriptional regulator of Treg cell differentiation, was markedly increased (P < 0.05). In contrast, the expression of RORC(γt), a transcription factor critical for Th17 cell differentiation, showed significant reduction after 72 h of TPx induction (P < 0.05).

The TGF-β/Smad signaling pathway is a crucial molecular mechanism involved in the imbalance of Treg/Th17 cells induced by the TPx protein of T. solium metacestode.

The TPx protein of Cysticercus cellulosae regulates the expression levels of Foxp3 and RORC (γt) by activating the TGF-β/Smad signaling pathway. Early (24 h) differentiation of Treg cells is slightly inhibited, while differentiation of Treg cells is promoted and differentiation of Th17 cells is inhibited in the mid to late stages (48 h, 72 h). This leads to an imbalance of host Treg/Th17 cells, resulting in an immune response predominantly characterized by Treg cells. This study primarily investigates the effects of the TPx protein on the differentiation of Treg and Th17 cells and its correlation with the TGF-β/Smad signaling pathway, providing important scientific evidence for further exploration of the immunopathogenesis of Cysticercosis.Illustration of TGF-beta signaling pathway at 0, 24, 48, and 72 hours showing Smad2/3 and Smad4 interaction. Graph depicts expression changes in Foxp3 and ROR-gamma-t, influencing Treg and Th17 cells. Results indicate shifts in immune tolerance and inflammation through TGF-beta, IL-10, and IL-17 expression levels.

The TPx protein of Cysticercus cellulosae regulates the expression levels of Foxp3 and RORC (γt) by activating the TGF-β/Smad signaling pathway. Early (24 h) differentiation of Treg cells is slightly inhibited, while differentiation of Treg cells is promoted and differentiation of Th17 cells is inhibited in the mid to late stages (48 h, 72 h). This leads to an imbalance of host Treg/Th17 cells, resulting in an immune response predominantly characterized by Treg cells. This study primarily investigates the effects of the TPx protein on the differentiation of Treg and Th17 cells and its correlation with the TGF-β/Smad signaling pathway, providing important scientific evidence for further exploration of the immunopathogenesis of Cysticercosis.