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The Type 1 Diabetes Locus Idd6 Controls TLR1 Expression.


Grimm,  Christina H.
Max Planck Society;

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Vallois, D., Grimm, C. H., Avner, P., Boitard, C., & Rogner, U. C. (2007). The Type 1 Diabetes Locus Idd6 Controls TLR1 Expression. The Journal of Immunology, 179(6), 3896-3903. Retrieved from

The Idd6 locus on mouse chromosome 6, which controls the development of type 1 diabetes in the NOD mouse, affects proliferation rates of T cells and the activity of regulatory CD4+CD25+ T cells. Using a transcriptional profiling approach, we show that splenocytes and thymocytes from diabetes-resistant Idd6 NOD.C3H-congenic mouse strains exhibit a constitutive and specific down-regulation of Toll-like receptor 1 (Tlr1) gene expression compared with diabetes prone NOD mice. This phenotype correlates with a diminished proliferation capacity of both CD4+CD25– effector and CD4+CD25+ regulatory T cells upon in vitro stimulation of the TLR1/TLR2 pathway by the ligand palmitoyl-3-cysteine-serine-lysine 4, and with the constitutive down-regulation of Tnf-{alpha} and IL-6 in macrophages of Idd6- congenic mice. These data suggest that TLR1 is involved in the regulation of mechanisms that impinge on diabetes development in the NOD mouse