期刊
JOURNAL OF IMMUNOLOGY
卷 178, 期 1, 页码 280-290出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.1.280
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- NHLBI NIH HHS [HL63452, HL56067] Funding Source: Medline
- NIAID NIH HHS [2T32-AI07313, AI34495] Funding Source: Medline
IL-2(-/-) mice develop autoimmunity despite having relatively normal numbers of regulatory T cells (Tregs). In contrast, we demonstrate that IL-2(-/-) X IL-15(-/-) and IL-2R beta(-/-) mice have a significant decrease in Treg numbers. Ectopic expression of foxp3 in a subset of CD4(+) T cells rescued Treg development and prevented autoimmunity in IL-2R beta(-/-) mice, suggesting that IL-2R beta-dependent signals regulate foxp3 expression in Tregs. Subsequent analysis of IL-2R beta-dependent signal transduction pathways established that the transcription factor STAT5 is necessary and sufficient for Treg development. Specifically, T cell-specific deletion of STAT5 prevented Treg development; conversely, reconstitution of IL-2R beta(-/-) mice with bone marrow cells expressing an IL-2R beta mutant that exclusively activates STAT5 restored Treg development. Finally, STAT5 binds to the promoter of the foxp3 gene suggesting that IL-2R beta-dependent STAT5 activation promotes Treg differentiation by regulating expression of foxp3.
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