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- Title
The Critical Roles of IL-2 in iNKT Cell Mediated Tolerance.
- Authors
Jie, Hyun-Bae; Lin, Henry; Lee, Hyeongwoo; Wilson, Brian; Viener, Hilla-Lee; Brusko, Todd; Wasserfall, Clive; Clare-Salzler, Michael; Atkinson, Mark A.
- Abstract
iNKT cells play critical roles in controlling autoimmune diseases including T1D. Here, we demonstrate that a-GalCer stimulation induces Foxp3 in human iNKT cells. Following a-GalCer stimulation, CD25 expression is upregulated followed by Foxp3 expression and proliferation of iNKT cells in a process that is dependent on IL-2 and STAT5. Blocking IL-2 or STAT5 signaling abrogates CD25-dependent expansion and results in the loss of Foxp3 expression by iNKT cells. Theses data suggest that TCR and IL-2 signaling pathways contribute to induction or maintenance of Foxp3 in iNKT cells. Importantly, activated CD4+ iNKT cells very effectively induce expansion of CD4+CD25+Foxp3+ (Treg) from CD4+CD25-Foxp3- cells in an IL-2 and APC-dependent manner. Furthermore, IL-4 and IFN-g, which are hallmark cytokines produced by iNKT cells, respectively prevent expansion and generation of Th17 T cells. Taken together, this suggests a mechanism whereby iNKT cells control autoimmune diseases by concomitantly inducing Tregs and suppressing Th17 cells thought to be important in the pathogenesis of autoimmunity.
- Subjects
KILLER cells; AUTOIMMUNE diseases; DIABETES; T cells; CELLS
- Publication
Diabetes, 2007, Vol 56, pA82
- ISSN
0012-1797
- Publication type
Article