Circulating CD4 regulatory T cells are broadly preserved in Parkinson's disease despite altered HELIOS expression
- 1University of Cambridge
Abstract
Background Regulatory T cells (Tregs) are an important component of adaptive immune regulation and have been implicated in Parkinson's disease (PD), with previous studies suggesting altered Treg proportions, phenotype and, in some cases, function. However, existing studies have been limited by variable phenotyping approaches and a lack of detailed functional assessment. Given the growing interest in Tregs as potential therapies in PD, better understanding of their phenotype and function in the disease is important. Methods Circulating FOXP3+ Tregs were characterised in individuals with PD and age-matched healthy controls (HC) using a 24-colour spectral flow cytometry panel. Treg suppressive function was assessed by their ability to inhibit proliferation and cytokine production by polyclonally stimulated autologous T effector cells in vitro. Treg lineage stability was assessed by analysis of FOXP3 TSDR demethylation. Results The proportions and phenotypic characteristics of circulating CD4 Tregs were broadly similar between individuals with PD and HCs, as were Treg suppressive function and FOXP3 TSDR demethylation. However, naive CD4 Tregs from individuals with PD showed reduced HELIOS expression, with a similar but non-significant trend in FOXP3 expression. Reduced HELIOS expression was also observed in the CD8 naive Treg compartment. Conclusions Major quantitative or functional abnormalities in circulating Tregs do not appear to be a dominant feature PD. However, reduced HELIOS expression in naive Tregs suggests more subtle phenotypic alterations that warrant further investigation. The broadly preserved suppressive function is reassuring for therapeutic approaches aimed at increasing Treg numbers, although it will be important to establish that expanded Tregs retain a stable phenotype and suppressive function in inflammatory and tissue environments.
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BibTeX
@misc{crooks2026circulating,
title = {{Circulating CD4 regulatory T cells are broadly preserved in Parkinson's disease despite altered HELIOS expression}},
author = {S. C. Crooks and A. Prabhu and L. B. Jarvis and Z. G. Georgieva and D. B. Rainbow and C. H. Williams-Gray and J. L. Jones},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.764595},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.764595v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Circulating CD4 regulatory T cells are broadly preserved in Parkinson's disease despite altered HELIOS expression
AU - S. C. Crooks
AU - A. Prabhu
AU - L. B. Jarvis
AU - Z. G. Georgieva
AU - D. B. Rainbow
AU - C. H. Williams-Gray
AU - J. L. Jones
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.764595
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.764595v1
AB - Background Regulatory T cells (Tregs) are an important component of adaptive immune regulation and have been implicated in Parkinson's disease (PD), with previous studies suggesting altered Treg proportions, phenotype and, in some cases, function. However, existing studies have been limited by variable phenotyping approaches and a lack of detailed functional assessment. Given the growing interest in Tregs as potential therapies in PD, better understanding of their phenotype and function in the disease is important. Methods Circulating FOXP3+ Tregs were characterised in individuals with PD and age-matched healthy controls (HC) using a 24-colour spectral flow cytometry panel. Treg suppressive function was assessed by their ability to inhibit proliferation and cytokine production by polyclonally stimulated autologous T effector cells in vitro. Treg lineage stability was assessed by analysis of FOXP3 TSDR demethylation. Results The proportions and phenotypic characteristics of circulating CD4 Tregs were broadly similar between individuals with PD and HCs, as were Treg suppressive function and FOXP3 TSDR demethylation. However, naive CD4 Tregs from individuals with PD showed reduced HELIOS expression, with a similar but non-significant trend in FOXP3 expression. Reduced HELIOS expression was also observed in the CD8 naive Treg compartment. Conclusions Major quantitative or functional abnormalities in circulating Tregs do not appear to be a dominant feature PD. However, reduced HELIOS expression in naive Tregs suggests more subtle phenotypic alterations that warrant further investigation. The broadly preserved suppressive function is reassuring for therapeutic approaches aimed at increasing Treg numbers, although it will be important to establish that expanded Tregs retain a stable phenotype and suppressive function in inflammatory and tissue environments.
ER -