PD-L1– and calcitriol-dependent liposomal antigen-specific regulation of systemic inflammatory autoimmune disease Article Swipe
Ryan Galea
,
Hendrik J. Nel
,
Meghna Talekar
,
Xiao Liu
,
Joshua D. Ooi
,
Megan Huynh
,
Sara Hadjigol
,
Kate Robson
,
Yi Tian Ting
,
Suzanne Cole
,
Karyn Cochlin
,
Shannon Hitchcock
,
Bijun Zeng
,
Suman Yekollu
,
Martine A. 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 O’Sullivan
,
Ranjeny Thomas
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.126025
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.126025
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.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1172/jci.insight.126025
- http://insight.jci.org/articles/view/126025/files/pdf
- OA Status
- gold
- Cited By
- 62
- References
- 68
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2971979367
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2971979367Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1172/jci.insight.126025Digital Object Identifier
- Title
-
PD-L1– and calcitriol-dependent liposomal antigen-specific regulation of systemic inflammatory autoimmune diseaseWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-09-05Full publication date if available
- Authors
-
Ryan Galea, Hendrik J. Nel, Meghna Talekar, Xiao Liu, Joshua D. Ooi, Megan Huynh, Sara Hadjigol, Kate Robson, Yi Tian Ting, Suzanne Cole, Karyn Cochlin, Shannon Hitchcock, Bijun Zeng, Suman Yekollu, Martine A. 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 O’Sullivan, Ranjeny ThomasList of authors in order
- Landing page
-
https://doi.org/10.1172/jci.insight.126025Publisher landing page
- PDF URL
-
https://insight.jci.org/articles/view/126025/files/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://insight.jci.org/articles/view/126025/files/pdfDirect OA link when available
- Concepts
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Calcitriol, Medicine, Liposome, Disease, Immunology, Cancer research, Internal medicine, Chemistry, Vitamin D and neurology, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
62Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 8, 2023: 15, 2022: 11, 2021: 15Per-year citation counts (last 5 years)
- References (count)
-
68Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.in | 85, 131, 152, 195 |
| abstract_inverted_index.is | 31 |
| abstract_inverted_index.of | 67, 87, 95, 105, 122, 163, 172 |
| abstract_inverted_index.on | 138 |
| abstract_inverted_index.to | 32, 39, 64, 90 |
| abstract_inverted_index.DCs | 54, 71, 104, 147 |
| abstract_inverted_index.MHC | 4, 111 |
| abstract_inverted_index.and | 19, 61, 72, 78, 99, 108, 120, 124, 127, 148, 157, 166, 178, 191 |
| abstract_inverted_index.dLN | 102 |
| abstract_inverted_index.for | 186 |
| abstract_inverted_index.the | 12, 161 |
| abstract_inverted_index.was | 83, 136 |
| abstract_inverted_index.CD40 | 143 |
| abstract_inverted_index.Treg | 150 |
| abstract_inverted_index.cell | 9, 176, 189 |
| abstract_inverted_index.dLNs | 86 |
| abstract_inverted_index.from | 3 |
| abstract_inverted_index.mice | 107 |
| abstract_inverted_index.node | 51 |
| abstract_inverted_index.used | 69 |
| abstract_inverted_index.with | 24, 170 |
| abstract_inverted_index.(dLN) | 52 |
| abstract_inverted_index.PD-L1 | 81, 185 |
| abstract_inverted_index.Teffs | 123 |
| abstract_inverted_index.Tregs | 130 |
| abstract_inverted_index.While | 21 |
| abstract_inverted_index.cells | 37, 75 |
| abstract_inverted_index.class | 5, 112 |
| abstract_inverted_index.human | 146 |
| abstract_inverted_index.lymph | 50 |
| abstract_inverted_index.mice. | 92 |
| abstract_inverted_index.naive | 91 |
| abstract_inverted_index.their | 110 |
| abstract_inverted_index.under | 76 |
| abstract_inverted_index.using | 55 |
| abstract_inverted_index.which | 135 |
| abstract_inverted_index.Foxp3+ | 126 |
| abstract_inverted_index.IL-10+ | 128 |
| abstract_inverted_index.PD-L1. | 139 |
| abstract_inverted_index.drugs, | 27 |
| abstract_inverted_index.induce | 192 |
| abstract_inverted_index.memory | 174 |
| abstract_inverted_index.models | 169 |
| abstract_inverted_index.vitro. | 153 |
| abstract_inverted_index.(Teffs) | 38 |
| abstract_inverted_index.PD-L1hi | 103 |
| abstract_inverted_index.antigen | 45 |
| abstract_inverted_index.include | 11 |
| abstract_inverted_index.induced | 125 |
| abstract_inverted_index.manner, | 134 |
| abstract_inverted_index.peptide | 63 |
| abstract_inverted_index.reduced | 109 |
| abstract_inverted_index.resting | 77 |
| abstract_inverted_index.restore | 40 |
| abstract_inverted_index.treated | 23 |
| abstract_inverted_index.diseases | 1 |
| abstract_inverted_index.draining | 49 |
| abstract_inverted_index.effector | 35 |
| abstract_inverted_index.function | 121 |
| abstract_inverted_index.immunity | 10 |
| abstract_inverted_index.leverage | 183 |
| abstract_inverted_index.peptides | 159 |
| abstract_inverted_index.promoted | 149 |
| abstract_inverted_index.regulate | 33 |
| abstract_inverted_index.relative | 89 |
| abstract_inverted_index.severity | 162 |
| abstract_inverted_index.strategy | 30 |
| abstract_inverted_index.systemic | 13 |
| abstract_inverted_index.targeted | 48, 101 |
| abstract_inverted_index.Liposomes | 154 |
| abstract_inverted_index.antigenic | 62 |
| abstract_inverted_index.arthritis | 18, 165 |
| abstract_inverted_index.currently | 22 |
| abstract_inverted_index.dependent | 137 |
| abstract_inverted_index.diseases. | 198 |
| abstract_inverted_index.elucidate | 65 |
| abstract_inverted_index.function. | 179 |
| abstract_inverted_index.immunized | 79, 88, 106 |
| abstract_inverted_index.induction | 151 |
| abstract_inverted_index.liposomes | 56, 96, 116, 141, 182 |
| abstract_inverted_index.modulated | 142 |
| abstract_inverted_index.resulting | 2 |
| abstract_inverted_index.tolerance | 41, 68, 194 |
| abstract_inverted_index.Autoimmune | 0 |
| abstract_inverted_index.OVA323-339 | 98 |
| abstract_inverted_index.autoimmune | 15, 197 |
| abstract_inverted_index.calcitriol | 100, 156 |
| abstract_inverted_index.conditions | 16 |
| abstract_inverted_index.expansion, | 118 |
| abstract_inverted_index.exploiting | 43 |
| abstract_inverted_index.expression | 82, 144 |
| abstract_inverted_index.mechanisms | 66 |
| abstract_inverted_index.peripheral | 129 |
| abstract_inverted_index.phagocytic | 53 |
| abstract_inverted_index.preferable | 29 |
| abstract_inverted_index.regulation | 190 |
| abstract_inverted_index.responding | 73 |
| abstract_inverted_index.rheumatoid | 17, 164 |
| abstract_inverted_index.suppressed | 117, 160 |
| abstract_inverted_index.vasculitis | 168 |
| abstract_inverted_index.conditions. | 80 |
| abstract_inverted_index.expression. | 114 |
| abstract_inverted_index.suppression | 171 |
| abstract_inverted_index.upregulated | 84 |
| abstract_inverted_index.vasculitis. | 20 |
| abstract_inverted_index.(calcitriol) | 60 |
| abstract_inverted_index.Accordingly, | 180 |
| abstract_inverted_index.Subcutaneous | 93 |
| abstract_inverted_index.broad-acting | 25 |
| abstract_inverted_index.inflammatory | 14, 196 |
| abstract_inverted_index.Goodpasture's | 167 |
| abstract_inverted_index.II-restricted | 6 |
| abstract_inverted_index.encapsulating | 57, 97, 155 |
| abstract_inverted_index.presentation. | 46 |
| abstract_inverted_index.administration | 94 |
| abstract_inverted_index.differentiation | 177 |
| abstract_inverted_index.antigen-specific | 34, 133, 173, 187, 193 |
| abstract_inverted_index.differentiation, | 119 |
| abstract_inverted_index.immunosuppressive | 26 |
| abstract_inverted_index.Peptide/calcitriol | 140 |
| abstract_inverted_index.disease-associated | 158 |
| abstract_inverted_index.peptide/calcitriol | 181 |
| abstract_inverted_index.autoantigen-specific | 7 |
| abstract_inverted_index.OVA323-339/calcitriol | 115 |
| abstract_inverted_index.1α,25-dihydroxyvitamin | 58 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5060328058 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 27 |
| corresponding_institution_ids | https://openalex.org/I165143802 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8299999833106995 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.91932723 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |