Work

In Vivo Augmentation of Regulatory T-Cell Function for the Treatment of Immune-mediated Diseases 2295

Year: 2025

Type: article

Abstract: Description Regulatory T cells (Tregs) are the most promising therapies for autoimmune diseases without compromising immune defense mechanisms. Adoptive transfer of Tregs generated ex vivo faces various challenges in human patients. Hence, we propose providing signals sufficient to stimulate Tregs in vivo by countering the proinflammatory tissue environment. Our published data have demonstrated that dendritic cells (DCs), capable of de novo synthesizing high concentrations of the active vitamin D (DC-CYP cells), stimulate Foxp3+ CD4+ Tregs in healthy mice and the mice induced for autoimmune diseases without significant side effects and that DCs, capable of de novo synthesizing both the active vitamin D and retinoic acid (DC-CYP-ALDH cells), stimulate Foxp3+ CD4+ Tregs that also express the gut-homing receptors CCR9 and alph4beta7 (gut-homing Tregs) in healthy mice and the mice induced for experimental colitis (an animal model of inflammatory bowel disease, IBD). Hence, both engineered DCs appear to overcome proinflammatory challenges in vivo. To evaluate their potential clinical applications, this study compared the engineered DCs from healthy subjects and IBD patients in stimulating Tregs. We show that the DC-CYP cells stimulate Foxp3+CCR9+ Tregs, and the DC-CYP-ALDH cells stimulate both Foxp3+CCR9+ and Foxp3+alph4beta7+ Tregs. Because the DC-CYP-ALDH cells stimulate both gut-homing Tregs, our data indicates that the DC-CYP-ALDH cells are a more promising in vivo therapy for IBD. Funding Sources This study was partially supported by the AAI Careers in Immunology Fellowship and the US Army Medical Research and Materiel Command grant (W81XWH-15-0240). Topic Categories Mucosal and Regional Immunology (MUC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.230

Authors: Nisar Ali Shaikh, Maisa I Abdalla, Diana Tang, David J Baylink, Xiaolei Tang

Institutions: Long Island University, University of Rochester Medicine, Loma Linda University

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: Medical Research and Materiel Command