The type 1 diabetes locus Idd6 controls TLR1 expression.
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.
Vallois
David
D
Unité de Génétique Moléculaire Murine Centre National de la Recherche Scientifique, Unité de Recherche Associée 2578, Institut Pasteur, Paris, France.
Grimm
Christina H
CH
Avner
Philip
P
Boitard
Christian
C
Rogner
Ute Christine
UC
D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D016688:Mice, Inbred NOD; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D011236:Prediabetic State / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051194:Toll-Like Receptor 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology