Parkinson's disease (PD) patients frequently exhibit vitamin D deficiency and an imbalance in T helper 17 (Th17) and regulatory T (Treg) cells, which may contribute to disease pathogenesis. Preclinical evidence suggests vitamin D regulates Th17/Treg balance, but the therapeutic effects of supplementation in PD remain unestablished. This randomized controlled trial investigated peripheral blood levels of vitamin D, Treg, and Th17 cells in PD patients, examined their associations with clinical outcomes, and assessed vitamin D3 supplementation's effects on immunological and motor functions. In this randomized, double-blind, placebo-controlled trial, 51 PD patients and 50 healthy controls (HCs) were enrolled. Thirty PD patients with vitamin D deficiency were randomized to receive vitamin D3 (n = 15) or placebo (vegetable oil, n = 15) for three months. Serum 25(OH)D3 levels were measured by electrochemiluminescence, and Th17/Treg cells were analyzed by flow cytometry. Motor and non-motor symptoms were assessed using standardized scales. Vitamin D3 supplementation significantly increased 25(OH)D3 levels (p < 0.05), reduced Th17 cells (4.62 ± 1.09 to 3.25 ± 1.14, p = 0.003), and elevated Tregs (3.25 ± 0.90 to 4.52 ± 0.95, p = 0.003). Motor function (UPDRS and UPDRS-III) improved in the vitamin D3 group (p < 0.001), while no changes were observed in the placebo group. This preliminary study suggests that vitamin D3 supplementation may restore Th17/Treg balance and potentially alleviate motor symptoms in vitamin D-deficient PD patients, indicating a possible therapeutic strategy.Trial registration: ClinicalTrials.gov: NCT:06539260. Registered 05 August 2024 - Retrospectively registered, https://clinicaltrials.gov/study/NCT06539260 .
© 2025. The Author(s).

The primary outcome was the evaluation of the T-cell phenotype in autoimmune primary adrenal insufficiency (PAI). Secondary outcomes included the evaluation of the CD4+CD25+Foxp3+ Treg population and the gene expression levels of IL-6, IL-17A, cyclooxygenase (COX)-2, heat shock proteins (HSP)-70, indoleamine-2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1), inducible nitric oxide synthase (iNOS), and thioredoxin (TXN)-1.
We prospectively included 15 patients with PAI on conventional glucocorticoid (GC) replacement therapy, 15 switched to dual-release hydrocortisone (DR-HC), and 20 healthy controls. Serum inflammatory parameters and peripheral blood mononuclear cells (PBMCs) were evaluated at baseline and after 12 months of treatment.
At baseline, significantly higher CD4+ and CD8+ (both p < 0.001) T-cell percentages, a lower CD4+/CD8+ ratio (p < 0.05), and higher CD25+ and CD4+/CD25+ T cells (both p < 0.001) were observed in PAI compared to controls. After 12 months of DR-HC treatment, we found significantly lower IL-6 (p = 0.019), IL-17A (p = 0.046), COX-2 (p < 0.001), HSP-70 (p = 0.006), and TXN-1 (p = 0.008) and higher PD-L1 (p < 0.001) and IDO (p < 0.001) mRNA values compared to baseline. After 12 months of DR-HC treatment, a significant increase in CD4+ T cells (p = 0.012), PD-L1 (p = 0.003), and IDO (p < 0.001) and a decrease in CD8+ T cells (p < 0.001), IL-6 (p = 0.003), IL-17A (p = 0.0014), COX-2 (p < 0.001), HSP-70 (p = 0.005), and TXN-1 (p = 0.0008), as well as a significantly higher conversion in the CD4+/CD8+ ratio (p = 0.033), were observed compared to conventional GCs.
The switch from conventional GCs to DR-HC treatment altered the T lymphocyte phenotype and CD4+/CD8+ ratio in a Treg-independent manner, inducing significant improvements in the immune and inflammatory profile in PAI.
Copyright © 2025 Tomasello, Coppola, Pizzolanti, Giordano, Arnaldi and Guarnotta.

Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.