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Citations to this article

PD-L1– and calcitriol-dependent liposomal antigen-specific regulation of systemic inflammatory autoimmune disease
Ryan Galea, … , Brendan J. O’Sullivan, Ranjeny Thomas
Ryan Galea, … , Brendan J. O’Sullivan, Ranjeny Thomas
Published September 5, 2019
Citation Information: JCI Insight. 2019;4(18):e126025. https://doi.org/10.1172/jci.insight.126025.
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Research Article Nephrology Article has an altmetric score of 75

PD-L1– and calcitriol-dependent liposomal antigen-specific regulation of systemic inflammatory autoimmune disease

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Abstract

Autoimmune diseases resulting from MHC class II–restricted autoantigen-specific T cell immunity include the systemic inflammatory autoimmune conditions rheumatoid arthritis and vasculitis. While currently treated with broad-acting immunosuppressive drugs, a preferable strategy is to regulate antigen-specific effector T cells (Teffs) to restore tolerance by exploiting DC antigen presentation. We targeted draining lymph node (dLN) phagocytic DCs using liposomes encapsulating 1α,25-dihydroxyvitamin D3 (calcitriol) and antigenic peptide to elucidate mechanisms of tolerance used by DCs and responding T cells under resting and immunized conditions. PD-L1 expression was upregulated in dLNs of immunized relative to naive mice. Subcutaneous administration of liposomes encapsulating OVA323–339 and calcitriol targeted dLN PD-L1hi DCs of immunized mice and reduced their MHC class II expression. OVA323–339/calcitriol liposomes suppressed expansion, differentiation, and function of Teffs and induced Foxp3+ and IL-10+ peripheral Tregs in an antigen-specific manner, which was dependent on PD-L1. Peptide/calcitriol liposomes modulated CD40 expression by human DCs and promoted Treg induction in vitro. Liposomes encapsulating calcitriol and disease-associated peptides suppressed the severity of rheumatoid arthritis and Goodpasture’s vasculitis models with suppression of antigen-specific memory T cell differentiation and function. Accordingly, peptide/calcitriol liposomes leverage DC PD-L1 for antigen-specific T cell regulation and induce antigen-specific tolerance in inflammatory autoimmune diseases.

Authors

Ryan Galea, Hendrik J. Nel, Meghna Talekar, Xiao Liu, Joshua D. Ooi, Megan Huynh, Sara Hadjigol, Kate J. Robson, Yi Tian Ting, Suzanne Cole, Karyn Cochlin, Shannon Hitchcock, Bijun Zeng, Suman Yekollu, Martine Boks, Natalie Goh, Helen Roberts, Jamie Rossjohn, Hugh H. Reid, Ben J. Boyd, Ravi Malaviya, David J. Shealy, Daniel G. Baker, Loui Madakamutil, A. Richard Kitching, Brendan J. O’Sullivan, Ranjeny Thomas

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 Total
Citations: 2 4 7 6 9 4 32
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Citations to this article (32)

Title and authors Publication Year
Current status of xenotransplantation from an immunobiological standpoint
Ko J, Lee G, Kim HW, Kang M, Kim HJ, Park CG
Clinical Transplantation and Research 2025
Intradermally Administered Retinoic Acid or Vitamin D3-Loaded Liposomes Induce Tolerogenic Skin Dendritic Cells
Nagy NA, Celant SG, van Capel TM, Sparrius R, Lozano Vigario F, van Ree R, Slütter B, Geijtenbeek TB, Tas SW, de Jong EC
Journal of Immunology Research 2025
High-throughput screening identification of novel immunomodulatory combinations for the generation of tolerogenic dendritic cells
Jia S, Kim J, Esser-Kahn AP, Deak P
Frontiers in Medicine 2024
The therapeutic potential of immunoengineering for systemic autoimmunity.
McBride DA, Jones RM, Bottini N, Shah NJ, McBride DA, Jones RM, Bottini N, Shah NJ
Nature reviews. Rheumatology 2024
Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines
Zimmerman DH, Szekanecz Z, Markovics A, Rosenthal KS, Carambula RE, Mikecz K
Frontiers in immunology 2024
Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders
Song Y, Li J, Wu Y
Signal Transduction and Targeted Therapy 2024
Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps
Carey ST, Bridgeman C, Jewell CM
Advanced Science 2023
Delivery route considerations for designing antigen-specific biomaterial strategies to combat autoimmunity.
Ackun-Farmmer MA, Jewell CM
2023
Counteracting Immunosenescence—Which Therapeutic Strategies Are Promising?
Hieber C, Grabbe S, Bros M
Biomolecules 2023
Advances in dendritic cell targeting nano-delivery systems for induction of immune tolerance
Lin G, Wang J, Yang YG, Zhang Y, Sun T
Frontiers in Bioengineering and Biotechnology 2023
Therapeutic induction of antigen-specific immune tolerance.
Kenison JE, Stevens NA, Quintana FJ
Nature reviews. Immunology 2023
Vaccines for immune tolerance against autoimmune disease.
Kim A, Xie F, Abed OA, Moon JJ
Advanced Drug Delivery Reviews 2023
Immunomodulatory nanoparticles for modulating arthritis flares
Johnson WT, McBride DA, Kerr MD, Nguyen A, Zoccheddu M, Bollmann M, Wei X, Jones RM, Wang W, Svensson MN, Bottini N, Shah NJ
ACS nano 2023
Nanoparticles for Inducing Antigen-Specific T Cell Tolerance in Autoimmune Diseases
N Benne, D ter Braake, A Stoppelenburg, F Broere
Frontiers in immunology 2022
Autoimmune disease and interconnections with vitamin D
J Fletcher, E Bishop, S Harrison, A Swift, S Cooper, S Dimeloe, K Raza, M Hewison
Endocrine Connections 2022
Randomized phase-1 trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis
Amee Sonigra, Hendrik J. Nel, Pascale Wehr, Nishta Ramnoruth, Swati Patel, Karin A. van Schie, Maxwell W. Bladen, Ahmed M. Mehdi, Joanne Tesiram, Meghna Talekar, Jamie Rossjohn, Hugh H. Reid, Frederik E Stuurman, Helen Roberts, Phillip Vecchio, Ian Gourley, Mark Rigby, Stephane Becart, Rene Toes, Hans U. Scherer, Kim-Anh Le Cao, Kim Campbell, Ranjeny Thomas
JCI Insight 2022
Immunomodulatory nano-preparations for rheumatoid arthritis
Li C, Han Y, Luo X, Qian C, Li Y, Su H, Du G
Drug Delivery 2022
Tissue-targeted drug delivery strategies to promote antigen-specific immune tolerance
Rui Y, Eppler HB, Yanes AA, Jewell CM
Advanced Healthcare Materials 2022
Robust tolerogenic dendritic cells via push/pull pairing of toll-like-receptor agonists and immunomodulators reduces EAE.
Deak P, Knight HR, Esser-Kahn A
Biomaterials 2022
Preclinical models of arthritis for studying immunotherapy and immune tolerance
GR Meehan, R Thomas, SA Khabouri, P Wehr, CM Hilkens, DC Wraith, D Sieghart, M Bonelli, G Nagy, P Garside, DF Tough, HD Lewis, JM Brewer
Annals of the rheumatic diseases 2021
Biomaterial-based immunotherapeutic strategies for rheumatoid arthritis
AB Tu, JS Lewis
Drug Delivery and Translational Research 2021
Immunologically Inert Nanostructures as Selective Therapeutic Tools in Inflammatory Diseases
L Talamini, E Matsuura, LD Cola, S Muller
Cells 2021
Potential for Antigen-Specific Tolerizing Immunotherapy in Systematic Lupus Erythematosus
S Robinson, R Thomas
Frontiers in immunology 2021
Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance
NA Nagy, AM de Haas, TB Geijtenbeek, R van Ree, SW Tas, Y van Kooyk, EC de Jong
Frontiers in immunology 2021
Evaluation of a fit-for-purpose assay to monitor antigen-specific functional CD4+ T cell subpopulations in rheumatoid arthritis using flow-cytometry based peptide-MHC class-II tetramer staining
S Patel, N Ramnoruth, P Wehr, J Rossjohn, HH Reid, K Campbell, HJ Nel, R Thomas
Clinical & Experimental Immunology 2021
Targeting DCs for Tolerance Induction: Don’t Lose Sight of the Neutrophils
FM Hafkamp, TG Kormelink, EC de Jong
Frontiers in immunology 2021
Manipulating antigen presentation for antigen-specific immunotherapy of autoimmune diseases
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Current Opinion in Immunology 2021
Recent Advances in Liposomal-Based Anti-Inflammatory Therapy
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Pharmaceutics 2021
Regulatory T Cells Induced by Single-Peptide Liposome Immunotherapy Suppress Islet-Specific T Cell Responses to Multiple Antigens and Protect from Autoimmune Diabetes
AS Bergot, I Buckle, S Cikaluru, JL Naranjo, CM Wright, G Zheng, M Talekar, EE Hamilton-Williams, R Thomas
Journal of immunology (Baltimore, Md. : 1950) 2020
Calcitriol inhibits osteoclastogenesis in an inflammatory environment by changing the proportion and function of T helper cell subsets (Th2/Th17)
CS Bi, X Li, HL Qu, LJ Sun, Y An, YL Hong, BM Tian, FM Chen
Cell Proliferation 2020
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