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Journal article
Synergistic Immunomodulatory Combinations Induce Robust Human Tolerogenic Dendritic Cells for Antigen-Specific Treg Generation
The journal of pharmacology and experimental therapeutics, v 393(6), Forthcoming
24 Apr 2026
PMID: 42184694
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
Restoring antigen-specific immune tolerance remains a central challenge in the treatment of autoimmune diseases, as conventional immunosuppressive therapies lack specificity and can compromise protective immunity. Tolerogenic dendritic cell (tolDC) therapies offer a promising strategy for inducing durable, antigen-specific regulatory T cell (Treg) responses, but current methods for generating tolDCs are limited by poor longevity and Treg generative capacity. This study evaluates the clinical potential of Push/Pull Immunomodulation (PPI), a novel combinatorial approach identified through high-throughput molecular screening, in human monocyte derived dendritic cells (moDCs). The phenotype, cytokine profile, and longevity of PPI-treated moDCs were benchmarked against conventional tolDC induction agents. Functional assays assessed the capacity of PPI-tolDCs to induce antigen-specific Tregs. PPI-treated moDCs exhibited increased expression of tolerogenic markers (IL-10, PD-L1, BTLA), enhanced in vitro longevity, and a unique transcriptomic signature characterized by upregulation of IDO1, IDO2, and T cell-sustaining cytokines. Notably, PPI9 induced robust, antigen-specific Treg responses, suggesting the potential for long-term tolerance induction. While transient TNFα release and moderate upregulation of CD40 and CD86 were observed, these did not impair Treg generation, indicating that PPI-tolDCs overcome key barriers associated with conventional tolDC therapies. Push/Pull Immunomodulation enables the generation of stable, long-lived human tolDCs with superior capacity to induce antigen-specific Tregs. Ongoing studies will further explore the translational potential of PPI-tolDCs for clinical applications in autoimmunity and transplantation.
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Details
- Title
- Synergistic Immunomodulatory Combinations Induce Robust Human Tolerogenic Dendritic Cells for Antigen-Specific Treg Generation
- Creators
- Sihan Jia - Drexel UniversityJoshua Chang Mell - Drexel University, Microbiology and ImmunologyPeter E Deak (Corresponding Author) - Drexel University, Chemical and Biological Engineering
- Publication Details
- The journal of pharmacology and experimental therapeutics, v 393(6), Forthcoming
- Publisher
- Elsevier
- Number of pages
- 14
- Grant note
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health: 1R21AI185460-01A1 Margaret Q. Landenberger Research Foundation
This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health [1R21AI185460-01A1] (to P.D.) and by the Margaret Q. Landenberger Research Foundation (to P.D.) .
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Chemical and Biological Engineering
- Web of Science ID
- WOS:001782042500001
- Scopus ID
- 2-s2.0-105039798141
- Other Identifier
- 991022172969004721