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Liposomal targeting of DCs to induce tolerance
- Source :
- Nature reviews. RheumatologyOriginal article. 15(12)
- Publication Year :
- 2019
-
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 OVA(323–339) and calcitriol targeted dLN PD-L1(hi) DCs of immunized mice and reduced their MHC class II expression. OVA(323–339)/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.
- Subjects :
- 0301 basic medicine
Anti-Glomerular Basement Membrane Disease
T-Lymphocytes
Pharmacology
medicine.disease_cause
Severity of Illness Index
B7-H1 Antigen
Autoimmunity
Immune tolerance
Arthritis, Rheumatoid
Mice
0302 clinical medicine
Antigen Presentation
Liposome
biology
FOXP3
Cell Differentiation
General Medicine
Adoptive Transfer
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
medicine.drug
Research Article
Calcitriol
Ovalbumin
T cell
Injections, Subcutaneous
Antigen presentation
Mice, Transgenic
chemical and pharmacologic phenomena
CHO Cells
Autoimmune Diseases
03 medical and health sciences
Cricetulus
Phagocytosis
Rheumatology
MHC class I
medicine
Immune Tolerance
Animals
Humans
Antigen-presenting cell
CD40
Immunodominant Epitopes
business.industry
HLA-DR Antigens
Dendritic Cells
Peptide Fragments
Disease Models, Animal
030104 developmental biology
Immunology
Liposomes
biology.protein
Lymph Nodes
business
Immunologic Memory
Subjects
Details
- ISSN :
- 17594804
- Volume :
- 15
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature reviews. RheumatologyOriginal article
- Accession number :
- edsair.doi.dedup.....fcc47b75f76cda7699c9976f3aaab335