Evidence of islet CADM1-mediated immune cell interactions during human type 1 diabetes Article Swipe
Chandan Sona
,
Yu‐Te Yeh
,
Andreas Patsalos
,
László Halász
,
Xin Yan
,
Natalia L. Kononenko
,
László Nagy
,
Matthew N. Poy
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.153136
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.153136
BACKGROUNDPathophysiology of type 1 diabetes (T1D) is illustrated by pancreatic islet infiltration of inflammatory lymphocytes, including CD8+ T cells; however, the molecular factors mediating their recruitment remain unknown. We hypothesized that single-cell RNA-sequencing (scRNA-Seq) analysis of immune cell populations isolated from islets of NOD mice captured gene expression dynamics providing critical insight into autoimmune diabetes pathogenesis.METHODSPancreatic sections from human donors were investigated, including individuals with T1D, autoantibody-positive (aAb+) individuals, and individuals without diabetes who served as controls. IHC was performed to assess islet hormones and both novel and canonical immune cell markers that were identified from unbiased, state-of-the-art workflows after reanalyzing murine scRNA-Seq data sets.RESULTSComputational workflows identified cell adhesion molecule 1-mediated (Cadm1-mediated) homotypic binding among the most important intercellular interactions among all cell clusters, as well as Cadm1 enrichment in macrophages and DCs from pancreata of NOD mice. Immunostaining of human pancreata revealed an increased number of CADM1+glucagon+ cells adjacent to CD8+ T cells in sections from T1D and aAb+ donors compared with individuals without diabetes. Numbers of CADM1+CD68+ peri-islet myeloid cells adjacent to CD8+ T cells were also increased in pancreatic sections from both T1D and aAb+ donors compared with individuals without diabetes.CONCLUSIONIncreased detection of CADM1+ cells adjacent to CD8+ T cells in pancreatic sections of individuals with T1D and those who were aAb+ validated workflows and indicated CADM1-mediated intercellular contact may facilitate islet infiltration of cytotoxic T lymphocytes and serve as a potential therapeutic target for preventing T1D pathogenesis.FUNDINGThe Johns Hopkins All Children's Foundation Institutional Research Grant Program, the National Natural Science Foundation of China (grant 82071326), and the Deutsche Forschungsgemeinschaft (grants 431549029-SFB1451, EXC2030-390661388, and 411422114-GRK2550).
Related Topics
Concepts
Islet
Immune system
Pathogenesis
Nod
CD8
Immunology
Type 1 diabetes
Diabetes mellitus
NOD mice
Biology
Pancreatic islets
Pathophysiology
Cell
Cell type
Gene
Endocrinology
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1172/jci.insight.153136
- http://insight.jci.org/articles/view/153136/files/pdf
- OA Status
- gold
- Cited By
- 20
- References
- 49
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4210928538
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4210928538Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1172/jci.insight.153136Digital Object Identifier
- Title
-
Evidence of islet CADM1-mediated immune cell interactions during human type 1 diabetesWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-02-08Full publication date if available
- Authors
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Chandan Sona, Yu‐Te Yeh, Andreas Patsalos, László Halász, Xin Yan, Natalia L. Kononenko, László Nagy, Matthew N. PoyList of authors in order
- Landing page
-
https://doi.org/10.1172/jci.insight.153136Publisher landing page
- PDF URL
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https://insight.jci.org/articles/view/153136/files/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://insight.jci.org/articles/view/153136/files/pdfDirect OA link when available
- Concepts
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Islet, Immune system, Pathogenesis, Nod, CD8, Immunology, Type 1 diabetes, Diabetes mellitus, NOD mice, Biology, Pancreatic islets, Pathophysiology, Cell, Cell type, Gene, Endocrinology, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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20Total citation count in OpenAlex
- Citations by year (recent)
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2025: 8, 2024: 7, 2023: 3, 2022: 2Per-year citation counts (last 5 years)
- References (count)
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49Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.to | 80, 150, 173, 199 |
| abstract_inverted_index.All | 243 |
| abstract_inverted_index.DCs | 132 |
| abstract_inverted_index.IHC | 77 |
| abstract_inverted_index.NOD | 43, 136 |
| abstract_inverted_index.T1D | 157, 185, 209, 239 |
| abstract_inverted_index.all | 121 |
| abstract_inverted_index.and | 69, 84, 87, 131, 158, 186, 210, 217, 230, 259, 266 |
| abstract_inverted_index.for | 237 |
| abstract_inverted_index.may | 222 |
| abstract_inverted_index.the | 20, 115, 250, 260 |
| abstract_inverted_index.was | 78 |
| abstract_inverted_index.who | 73, 212 |
| abstract_inverted_index.CD8+ | 16, 151, 174, 200 |
| abstract_inverted_index.T1D, | 65 |
| abstract_inverted_index.aAb+ | 159, 187, 214 |
| abstract_inverted_index.also | 178 |
| abstract_inverted_index.both | 85, 184 |
| abstract_inverted_index.cell | 37, 90, 107, 122 |
| abstract_inverted_index.data | 103 |
| abstract_inverted_index.from | 40, 57, 95, 133, 156, 183 |
| abstract_inverted_index.gene | 46 |
| abstract_inverted_index.into | 52 |
| abstract_inverted_index.mice | 44 |
| abstract_inverted_index.most | 116 |
| abstract_inverted_index.that | 30, 92 |
| abstract_inverted_index.type | 2 |
| abstract_inverted_index.well | 125 |
| abstract_inverted_index.were | 60, 93, 177, 213 |
| abstract_inverted_index.with | 64, 162, 190, 208 |
| abstract_inverted_index.(T1D) | 5 |
| abstract_inverted_index.Cadm1 | 127 |
| abstract_inverted_index.China | 256 |
| abstract_inverted_index.Grant | 248 |
| abstract_inverted_index.Johns | 241 |
| abstract_inverted_index.after | 99 |
| abstract_inverted_index.among | 114, 120 |
| abstract_inverted_index.cells | 148, 153, 171, 176, 197, 202 |
| abstract_inverted_index.human | 58, 140 |
| abstract_inverted_index.islet | 10, 82, 224 |
| abstract_inverted_index.mice. | 137 |
| abstract_inverted_index.novel | 86 |
| abstract_inverted_index.serve | 231 |
| abstract_inverted_index.their | 24 |
| abstract_inverted_index.those | 211 |
| abstract_inverted_index.(aAb+) | 67 |
| abstract_inverted_index.(grant | 257 |
| abstract_inverted_index.CADM1+ | 196 |
| abstract_inverted_index.assess | 81 |
| abstract_inverted_index.cells; | 18 |
| abstract_inverted_index.donors | 59, 160, 188 |
| abstract_inverted_index.immune | 36, 89 |
| abstract_inverted_index.islets | 41 |
| abstract_inverted_index.murine | 101 |
| abstract_inverted_index.number | 145 |
| abstract_inverted_index.remain | 26 |
| abstract_inverted_index.served | 74 |
| abstract_inverted_index.target | 236 |
| abstract_inverted_index.(grants | 263 |
| abstract_inverted_index.Hopkins | 242 |
| abstract_inverted_index.Natural | 252 |
| abstract_inverted_index.Numbers | 166 |
| abstract_inverted_index.Science | 253 |
| abstract_inverted_index.binding | 113 |
| abstract_inverted_index.contact | 221 |
| abstract_inverted_index.factors | 22 |
| abstract_inverted_index.insight | 51 |
| abstract_inverted_index.markers | 91 |
| abstract_inverted_index.myeloid | 170 |
| abstract_inverted_index.without | 71, 164, 192 |
| abstract_inverted_index.Deutsche | 261 |
| abstract_inverted_index.National | 251 |
| abstract_inverted_index.Program, | 249 |
| abstract_inverted_index.Research | 247 |
| abstract_inverted_index.adhesion | 108 |
| abstract_inverted_index.adjacent | 149, 172, 198 |
| abstract_inverted_index.analysis | 34 |
| abstract_inverted_index.captured | 45 |
| abstract_inverted_index.compared | 161, 189 |
| abstract_inverted_index.critical | 50 |
| abstract_inverted_index.diabetes | 4, 54, 72 |
| abstract_inverted_index.dynamics | 48 |
| abstract_inverted_index.hormones | 83 |
| abstract_inverted_index.however, | 19 |
| abstract_inverted_index.isolated | 39 |
| abstract_inverted_index.molecule | 109 |
| abstract_inverted_index.revealed | 142 |
| abstract_inverted_index.sections | 56, 155, 182, 205 |
| abstract_inverted_index.unknown. | 27 |
| abstract_inverted_index.canonical | 88 |
| abstract_inverted_index.clusters, | 123 |
| abstract_inverted_index.controls. | 76 |
| abstract_inverted_index.cytotoxic | 227 |
| abstract_inverted_index.detection | 194 |
| abstract_inverted_index.diabetes. | 165 |
| abstract_inverted_index.homotypic | 112 |
| abstract_inverted_index.important | 117 |
| abstract_inverted_index.including | 15, 62 |
| abstract_inverted_index.increased | 144, 179 |
| abstract_inverted_index.indicated | 218 |
| abstract_inverted_index.mediating | 23 |
| abstract_inverted_index.molecular | 21 |
| abstract_inverted_index.pancreata | 134, 141 |
| abstract_inverted_index.performed | 79 |
| abstract_inverted_index.potential | 234 |
| abstract_inverted_index.providing | 49 |
| abstract_inverted_index.scRNA-Seq | 102 |
| abstract_inverted_index.unbiased, | 96 |
| abstract_inverted_index.validated | 215 |
| abstract_inverted_index.workflows | 98, 105, 216 |
| abstract_inverted_index.1-mediated | 110 |
| abstract_inverted_index.82071326), | 258 |
| abstract_inverted_index.Children's | 244 |
| abstract_inverted_index.Foundation | 245, 254 |
| abstract_inverted_index.autoimmune | 53 |
| abstract_inverted_index.enrichment | 128 |
| abstract_inverted_index.expression | 47 |
| abstract_inverted_index.facilitate | 223 |
| abstract_inverted_index.identified | 94, 106 |
| abstract_inverted_index.pancreatic | 9, 181, 204 |
| abstract_inverted_index.peri-islet | 169 |
| abstract_inverted_index.preventing | 238 |
| abstract_inverted_index.(scRNA-Seq) | 33 |
| abstract_inverted_index.CADM1+CD68+ | 168 |
| abstract_inverted_index.illustrated | 7 |
| abstract_inverted_index.individuals | 63, 70, 163, 191, 207 |
| abstract_inverted_index.lymphocytes | 229 |
| abstract_inverted_index.macrophages | 130 |
| abstract_inverted_index.populations | 38 |
| abstract_inverted_index.reanalyzing | 100 |
| abstract_inverted_index.recruitment | 25 |
| abstract_inverted_index.single-cell | 31 |
| abstract_inverted_index.therapeutic | 235 |
| abstract_inverted_index.hypothesized | 29 |
| abstract_inverted_index.individuals, | 68 |
| abstract_inverted_index.infiltration | 11, 225 |
| abstract_inverted_index.inflammatory | 13 |
| abstract_inverted_index.interactions | 119 |
| abstract_inverted_index.lymphocytes, | 14 |
| abstract_inverted_index.Institutional | 246 |
| abstract_inverted_index.intercellular | 118, 220 |
| abstract_inverted_index.investigated, | 61 |
| abstract_inverted_index.CADM1-mediated | 219 |
| abstract_inverted_index.Immunostaining | 138 |
| abstract_inverted_index.RNA-sequencing | 32 |
| abstract_inverted_index.CADM1+glucagon+ | 147 |
| abstract_inverted_index.(Cadm1-mediated) | 111 |
| abstract_inverted_index.state-of-the-art | 97 |
| abstract_inverted_index.431549029-SFB1451, | 264 |
| abstract_inverted_index.EXC2030-390661388, | 265 |
| abstract_inverted_index.411422114-GRK2550). | 267 |
| abstract_inverted_index.autoantibody-positive | 66 |
| abstract_inverted_index.Forschungsgemeinschaft | 262 |
| abstract_inverted_index.pathogenesis.FUNDINGThe | 240 |
| abstract_inverted_index.BACKGROUNDPathophysiology | 0 |
| abstract_inverted_index.sets.RESULTSComputational | 104 |
| abstract_inverted_index.diabetes.CONCLUSIONIncreased | 193 |
| abstract_inverted_index.pathogenesis.METHODSPancreatic | 55 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5059678741 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 8 |
| corresponding_institution_ids | https://openalex.org/I145311948, https://openalex.org/I2799853436, https://openalex.org/I4210098865 |
| citation_normalized_percentile.value | 0.93697904 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |