Role of mast cells in innate and adaptive immune response

众所周知，肥大细胞是潜在威胁生命的过敏反应的媒介。人们对这些细胞的有益功能知之甚少。目前教科书上关于肥大细胞体内功能的大部分知识都来自于肥大细胞缺陷突变小鼠的实验，作为肥大细胞缺陷的模型，以及它们与体外分化的肥大细胞的重建。利用我们最近建立的基于Cre/loxP(不依赖试剂盒)的肥大细胞缺失和肥大细胞特异性基因失活的新模型，我们发现肥大细胞是T细胞对有机半抗原反应的重要促进器。这一发现与已发表的文献报道相矛盾，该报告基于对KIT突变小鼠的实验，肥大细胞抑制这些反应。我们的结论是，在KIT突变小鼠身上获得的结果，即使通过肥大细胞重建得到验证，也不一定能反映正常小鼠的情况。因此，我们认为肥大细胞是否在先天免疫中发挥了相关作用，以及T细胞和体液反应是否仍未解决这一重要问题。该项目的目的是重新研究肥大细胞在抵抗细菌病原体和适应性免疫反应的经典模型中的作用。

Mast cells are well known as mediators of potentially life-threatening anaphylaxis. Beneficial functions of these cells are far less understood. Most of current textbook knowledge on mast cell in vivo functions stems from experiments in mast cell-deficient kit mutant mice as models of mast cell-deficiency and their reconstitution with in vitro-differentiated mast cells. Using novel Cre/loxP-based (and kit independent) models of mast cell-deficiency and mast cellspecific gene inactivation, which we recently generated, we found that mast cells are essential promoters of the T cell response to organic haptens. This finding is at conflict with published literature reporting, based on experiments in kit mutant mice, that mast cells suppress these responses. We conclude that results obtained in kit mutant mice, even if validated by mast cell reconstitution, do not necessarily reflect the situation in normal mice. Therefore, we consider the important question whether mast cells play relevant roles in innate immunity as well as T cell and humoral responses still open. The aim of the project is to re-address the contribution of mast cells in classical models of innate defense against bacterial pathogens and adaptive immune responses.