Genetic and functional data identifying < i > Cd101 < /i > as a type 1 diabetes (T1D) susceptibility gene in nonobese diabetic (NOD) mice

by Jochen Mattner, Javid P. Mohammed, Michael E. Fusakio, Claudia Giessler, Carl-Philipp Hackstein, Robert Opoka, Marius Wrage, Regina Schey, Jan Clark, Heather I. Fraser, Daniel B. Rainbow, Linda S. Wicker Type 1 diabetes (T1D) is a chronic multi-factorial disorder characterized by the immune-mediated destruction of insulin-producing pancreatic beta cells. Variations at a large number of genes influence susceptibility to spontaneous autoimmune T1D in non-obese diabetic (NOD) mice, one of the most fr equently studied animal models for human disease. The genetic analysis of these mice allowed the identification of many insulin-dependent diabetes (Idd) loci and candidate genes, one of them beingCd101. CD101 is a heavily glycosylated transmembrane molecule which exhibits negative-costimulatory functions and promotes regulatory T (Treg) function. It is abundantly expressed on subsets of lymphoid and myeloid cells, particularly within the gastrointestinal tract. We have recently reported that the genotype-dependent expression of CD101 correlates with a decreased susceptibility to T1D in NOD.B6Idd10 congenic mice compared to parental NOD controls. Here we show that the knockout of CD101 within the introgressed B6-derivedIdd10 region increased T1D frequency to that of the NOD strain. This loss of protection from T1D was paralleled by decreased Gr1-expressing myeloid cells and FoxP3+ Tregs and an enhanced accumulation of CD4-positive over CD8-positive T lymphocytes in pancreatic tis...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research