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Cell Metab. 2017 Mar 7;25(3):727-738. doi: 10.1016/j.cmet.2017.01.005. Epub 2017 Feb 9.

β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice.

Author information

1
Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
2
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
3
Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
4
Department of Pathology, Yale University, New Haven, CT 06520, USA.
5
Department of Immunobiology, Yale University, New Haven, CT 06520, USA; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA. Electronic address: kevan.herold@yale.edu.

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune-mediated destruction of β cells. How β cells respond to immune attack is unknown. We identified a population of β cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal β cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of β cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes. This new subpopulation is resistant to killing when diabetes is precipitated with cyclophosphamide. Human β cells show similar changes when cultured with immune cells. These changes may account for the chronicity of the disease and the long-term survival of β cells in some patients.

KEYWORDS:

autoimmunity; immune regulation; stem cell; β cell

PMID:
28190773
PMCID:
PMC5342930
[Available on 2018-03-07]
DOI:
10.1016/j.cmet.2017.01.005
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