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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
Citation information
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Citations to this article in year 2021 (9)

Title and authors Publication Year
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
HB Streeter, DC Wraith
Current Opinion in Immunology 2021
Recent Advances in Liposomal-Based Anti-Inflammatory Therapy
CM van Alem, JM Metselaar, C van Kooten, JI Rotmans
Pharmaceutics 2021

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