A minor subset of Batf3-dependent antigen-presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes

Immunity. 2014 Oct 16;41(4):657-69. doi: 10.1016/j.immuni.2014.09.012.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, CD / biosynthesis*
  • Autoimmunity / immunology
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • CD8 Antigens / biosynthesis*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Epitopes / biosynthesis
  • Epitopes / immunology
  • Female
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / immunology
  • Homeodomain Proteins / genetics
  • Inflammation / immunology
  • Integrin alpha Chains / biosynthesis*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / immunology
  • Langerhans Cells / immunology*
  • Lymph Nodes / cytology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Pancreas / cytology
  • Repressor Proteins / genetics*
  • T-Lymphocytes / immunology


  • Antigens, CD
  • Basic-Leucine Zipper Transcription Factors
  • CD8 Antigens
  • CD8alpha antigen
  • Epitopes
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Homeodomain Proteins
  • Integrin alpha Chains
  • Repressor Proteins
  • SNFT protein, mouse
  • alpha E integrins
  • RAG-1 protein

Associated data

  • GEO/GSE61847