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Cited by 164Diabetes and associated disordersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

A Minor Subset of Batf3-Dependent Antigen-Presenting Cells in Islets of Langerhans Is Essential for the Development of Autoimmune Diabetes

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Ferris, Stephen T., Carrero, Javier A., Mohan, James F., Calderon, Boris, Murphy, Kenneth M., Unanue, Emil R.·2014·Immunity
DOI 10.1016/j.immuni.2014.09.012PMC PMC4220295
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Abstract

Autoimmune diabetes is characterized by inflammatory infiltration; however, the initiating events are poorly understood. We found that the islets of Langerhans in young nonobese diabetic (NOD) mice contained two antigen-presenting cell (APC) populations: a major macrophage and a minor CD103(+) dendritic cell (DC) population. By 4 weeks of age, CD4(+) T cells entered islets coincident with an increase in CD103(+) DCs. In order to examine the role of the CD103(+) DCs in diabetes, we examined Batf3-deficient NOD mice that lacked the CD103(+) DCs in islets and pancreatic lymph nodes. This led to a lack of autoreactive T cells in islets and, importantly, no incidence of diabetes. Additional examination revealed that presentation of major histocompatibility complex (MHC) class I epitopes in the pancreatic lymph nodes was absent with a partial impairment of MHC class II presentation. Altogether, this study reveals that CD103(+) DCs are essential for autoimmune diabetes development.

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  • β-cell-specific CD8 T cells in NOD mice are primed in the pancreatic draining lymph node (pLN) before they infiltrate the pancreas.

    “β-cell-specific CD8 T cells in NOD mice are primed in the pancreatic draining lymph node (pLN) before they infiltrate the pancreas6,11.”

    From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [11]

    The Results report proliferation of β-cell-antigen-specific 8.3 CD8+ T cells in the pancreatic lymph node of NOD mice, and the Discussion describes CD8+ T-cell priming there. The paper does not establish that these CD8+ T cells are primed before infiltrating the pancreas; in the reported transfer experiment, the 8.3 cells did not enter the islets. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Ferris, S. T., Carrero, J. A., Mohan, J. F., Calderon, B., Murphy, K. M., & Unanue, E. R.
Affiliations
  • Washington University in St. Louis (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Unanue, Emil R.
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2014-10
Volume
41
Issue
4
Pages
657-669
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2014.09.012
PMC
PMC4220295
OpenAlex
W2061265562
Cited by
164
References
2
Citations by year
2026: 8 · 2025: 18 · 2024: 11 · 2023: 14 · 2022: 8 · 2021: 13 · 2020: 17 · 2019: 12 · 2018: 11 · 2017: 22 · 2016: 16 · 2015: 14
FWCI
11.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5p60dk020579-35)
  • National Institute of Allergy and Infectious Diseases (T32AI007163)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK05817, DK‐020579, R01DK058177, P60-DK-020579, P30DK020579)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR048335)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
autoimmune diabetes, Batf3, CD103+ dendritic cells, pancreatic islets, antigen-presenting cells, NOD mice, CD4+ T cells, MHC class II presentation, pancreatic lymph nodes, autoreactive T cells, macrophages
MeSH terms
Animals, Epitopes, Histocompatibility Antigens Class II, Diabetes Mellitus, Type 1, Female, Inflammation, Islets of Langerhans, Langerhans Cells, Lymph Nodes, Macrophages, Pancreas, Repressor Proteins, T-Lymphocytes, Histocompatibility Antigens Class I, Autoimmunity, Antigens, CD, Mice, Inbred NOD, CD8 Antigens, Antigen Presentation, Mice, Knockout, Homeodomain Proteins, Integrin alpha Chains, Basic-Leucine Zipper Transcription Factors, Mice

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