Role of CD44 in the differentiation of Th1 and Th2 cells: CD44-deficiency enhances the development of Th2 effectors in response to sheep RBC and chicken ovalbumin.
Role of CD44 in the differentiation of Th1 and Th2 cells: CD44-deficiency enhances the development of Th2 effectors in response to sheep RBC and chicken ovalbumin.
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DOI：
10.4049/jimmunol.0802325
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发表时间：
2009-07-01
期刊：
影响因子：
--
通讯作者：
Nagarkatti M
中科院分区：
文献类型：
--
作者：
Guan H;Nagarkatti PS;Nagarkatti M
CD4 T 细胞可以主要极化以分化为 Th1 或 Th2 细胞。 CD44 是 T 细胞激活的标志物，也是长寿命记忆细胞的特性，与细胞迁移、激活和分化有关。迄今为止，CD44是否具有调节Th1-Th2分化的作用尚未确定。在这项研究中，我们比较了野生型和 CD44 缺陷型小鼠对 SRBC 和鸡卵清蛋白的 Th1 和 Th2 反应，并在体内和体外检查了 CD44 充足和 CD44 缺陷的幼稚 CD4 T 细胞的 Th1-Th2 分化。我们观察到 CD44 缺乏往往会抑制 Th1，同时促进 Th2 分化。此外，嵌合研究表明 CD4 T 细胞表达 CD44 对于这种 Th2 偏好至关重要。 CD44 的调节发生在转录水平，导致活化的 CD4 T 细胞中 GATA3 表达上调并下调 T-bet 表达。我们还注意到 CD44 缺陷可以改变树突状细胞亚群的状态，从而诱导 Th2 偏向的发育。本文的结果首次证明 CD44 参与 Th1-Th2 分化的调节。
CD4 T cells can be primarily polarized to differentiate into Th1 or Th2 cells. CD44 is a marker of T cell activation and a property of long-lived memory cells and implicated in cell migration, activation and differentiation. To date, whether CD44 has a role in regulating Th1-Th2 differentiation has not been determined. In this study, we compared Th1 and Th2 responses in wild-type and CD44-deficient mice in response to SRBC and chicken ovalbumin, as well as examined Th1-Th2 differentiation in vivo and in vitro from CD44-sufficient and CD44-deficient naïve CD4 T cells. We observed that deficiency of CD44 tended to inhibit Th1 while promoting Th2 differentiation. Furthermore, chimeric studies suggested that CD44 expression by CD4 T cells was essential for such Th2 bias. The regulation by CD44 occurred at the transcription level leading to up-regulated GATA3 and down-regulated T-bet expression in activated CD4 T cells. We also noted that CD44-deficiency could modify the state of dendritic cell subsets to induce a Th2-biased development. Results presented here demonstrate for the first time that CD44 participates in the regulation of Th1-Th2 differentiation.
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