IL-2 production by dendritic cells promotes Foxp3(+) regulatory T-cell expansion in autoimmune-resistant NOD congenic mice.
Il2 allelic variation in non-obese diabetic mice imparts marked resistance to type 1 diabetes. IL-2 is pivotal for the fitness and homeostasis of Foxp3(+) regulatory T (T(reg)) cells, and the Idd3(B6) locus augments IL-2 production by effector T cells, which in turn enhances the potency of T(reg) cell functions. Given the important role dendritic cells (DCs) play in T(reg) cell-mediated tolerance induction, we hypothesized that DCs from Idd3(B6) congenic mice contribute to increased T(reg) cell activity. Here, we observed that CD11c(+) DCs, harboring protective Idd3(B6) genes, are endowed with the capacity to secrete IL-2, enabling them to preferentially promote T(reg) cell functions in vitro and in vivo. Our results show that Il2 gene variation may imprint DCs to favor T-cell regulation of autoimmunity.
Departments of Microbiology & Immunology and Medicine, FOCIS Center of Excellence, McGill University and Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Evridiki
E
Sgouroudis
Mara
M
Kornete
Ciriaco A
CA
Piccirillo
D000483:Alleles; D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism*; D014644:Genetic Variation / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2