期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 10, 页码 3740-3745出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0600205103
关键词
IL-4; GATA-3
资金
- NIAID NIH HHS [AI50498, AI49453, R01 AI049453, P01 AI050498] Funding Source: Medline
T cell helper type 2(Th2)differentiation is driven by a source of IL-4 receptor (IL-4R) that mobilizes IL-4R signaling pathways and the transcription factor GATA-3. Naive CD4 cells can secrete IL-4 independently of IL-4R signals, but how this secretion is regulated is not understood. Here we demonstrate that costimulation through the tumor necrosis factor receptor family molecule OX40, in synergy with CD28, is essential for high levels of nuclear factor of activated T cells c1 to accumulate in the nucleus of a recently activated naive T cell. This action is not dependent on either IL-4R or IL-2R signals and results in OX40 controlling initial naive T cell IL-4 transcription. OX40 signals subsequently enhance nuclear GATA-3 accumulation through an IL-4R-dependent action, leading to Th2 differentiation. These data show that, in the absence of an exogenous source of IL-4, OX40 provides a critical synergistic and temporal signal with other noncytokine receptors to modulate nuclear factor of activated T cells c1 and to promote optimal Th2 generation.
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