Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ Mice

John D. Glawe, D. Ross Patrick, Meng Huang, Christopher Sharp, Shayne C. Barlow, Christopher G. Kevil

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

OBJECTIVE - Insulitis is an important pathological feature of autoimmune diabetes; however, mechanisms governing the recruitment of diabetogenic T-cells into pancreatic islets are poorly understood. Here, we determined the importance of leukocyte integrins β2 (Itgb2) and αL (ItgaL) in developing insulitis and frank diabetes. RESEARCH DESIGN AND METHODS - Gene-targeted mutations of either Itgb2 or ItgaL were established on the NOD/LtJ mouse strain. Experiments were performed to measure insulitis and diabetes development. Studies were also performed measuring mutant T-cell adhesion to islet microvascular endothelial cells under hydrodynamic flow conditions. T-cell adhesion molecule profiles and adoptive transfer studies were also performed. RESULTS - Genetic deficiency of either Itgb2 or ItgaL completely prevented the development of hyperglycemia and frank diabetes in NOD mice. Loss of Itgb2 or ItgaL prevented insulitis with Itgb2 deficiency conferring complete protection. In vitro hydrodynamic flow adhesion studies also showed that loss of Itgb2 completely abrogated T-cell adhesion. However, ItgaL deficiency did not alter NOD T-cell adhesion to or transmigration across islet endothelial cells. Adoptive transfer of ItgaL-deficient splenocytes into NOD/Rag-1 mice did not result in development of diabetes, suggesting a role for ItgaL in NOD/LtJ T-cell activation. CONCLUSIONS - Together, these data demonstrate that genetic deficiency of Itgb2 or ItgaL confers protection against autoimmune diabetes through distinctly different mechanisms.

Original languageEnglish (US)
Pages (from-to)1292-1301
Number of pages10
JournalDiabetes
Volume58
Issue number6
DOIs
StatePublished - Jun 1 2009

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Inbred NOD Mouse
Type 1 Diabetes Mellitus
T-Lymphocytes
Cell Adhesion
Adoptive Transfer
Hydrodynamics
Islets of Langerhans
Endothelial Cells
Cell Adhesion Molecules
Integrins
Hyperglycemia
Leukocytes
Research Design
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glawe, J. D., Patrick, D. R., Huang, M., Sharp, C., Barlow, S. C., & Kevil, C. G. (2009). Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ Mice. Diabetes, 58(6), 1292-1301. https://doi.org/10.2337/db08-0804

Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ Mice. / Glawe, John D.; Patrick, D. Ross; Huang, Meng; Sharp, Christopher; Barlow, Shayne C.; Kevil, Christopher G.

In: Diabetes, Vol. 58, No. 6, 01.06.2009, p. 1292-1301.

Research output: Contribution to journalArticle

Glawe, JD, Patrick, DR, Huang, M, Sharp, C, Barlow, SC & Kevil, CG 2009, 'Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ Mice', Diabetes, vol. 58, no. 6, pp. 1292-1301. https://doi.org/10.2337/db08-0804
Glawe, John D. ; Patrick, D. Ross ; Huang, Meng ; Sharp, Christopher ; Barlow, Shayne C. ; Kevil, Christopher G. / Genetic deficiency of Itgb2 or ItgaL prevents autoimmune diabetes through distinctly different mechanisms in NOD/LtJ Mice. In: Diabetes. 2009 ; Vol. 58, No. 6. pp. 1292-1301.
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