Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
Eur J Immunol. 2011 Nov;41(11):3198-207. doi: 10.1002/eji.201141521. Epub 2011 Sep 19.
CD44 is a cell adhesion molecule involved in lymphocyte infiltration of inflamed tissues. We previously demonstrated that CD44 plays an important role in the development of airway inflammation in a murine model of allergic asthma. In this study, we investigated the role of CD44 expressed on CD4(+) T cells in the accumulation of T-helper type 2 (Th2) cells in the airway using CD44-deficient mice and anti-CD44 monoclonal antibodies. Antigen-induced Th2-mediated airway inflammation and airway hyperresponsiveness (AHR) in sensitized mice were reduced by CD44-deficiency. These asthmatic responses induced by the transfer of antigen-sensitized splenic CD4(+) T cells from CD44-deficient mice were weaker than those from WT mice. Lack of CD44 failed to induce AHR by antigen challenge. Expression level and hyaluronic acid receptor activity of CD44, as well as Neu1 sialidase expression on antigen-specific Th2 cells, were higher than those on antigen-specific Th1 cells. Anti-CD44 antibody preferentially suppressed the accumulation of those Th2 cells in the airway induced by antigen challenge. Our findings indicate that CD44 expressed on CD4(+) T cells plays a critical role in the accumulation of antigen-specific Th2 cells, but not Th1 cells, in the airway and in the development of AHR induced by antigen challenge.
CD44 是一种参与淋巴细胞浸润炎症组织的细胞黏附分子。我们之前的研究表明，CD44 在变应性哮喘小鼠模型的气道炎症发展中起着重要作用。在这项研究中，我们使用 CD44 缺陷小鼠和抗 CD44 单克隆抗体，研究了 CD4(+) T 细胞上表达的 CD44 在气道中 2 型辅助性 T 细胞（Th2）细胞聚集中的作用。CD44 缺陷减少了抗原诱导的 Th2 介导的气道炎症和气道高反应性（AHR）。与 WT 小鼠相比，从 CD44 缺陷小鼠转移的抗原致敏脾 CD4(+) T 细胞诱导的这些哮喘反应较弱。缺乏 CD44 未能通过抗原挑战诱导 AHR。CD44 的表达水平和透明质酸受体活性，以及抗原特异性 Th2 细胞上 Neu1 神经氨酸酶的表达，均高于抗原特异性 Th1 细胞。抗 CD44 抗体优先抑制抗原挑战诱导的气道中这些 Th2 细胞的聚集。我们的研究结果表明，CD44 在 CD4(+) T 细胞上的表达在气道中抗原特异性 Th2 细胞的聚集，而不是 Th1 细胞的聚集，以及抗原挑战诱导的 AHR 发展中起着关键作用。
