哺乳动物的胶原蛋白含量非常丰富，约占总蛋白的25%-35%。胶原蛋白不仅负责维持组织的形态结构，而且在各种生理及病理过程中都有重要作用，其缺失或变异后会对机体产生严重影响，已知人类超过1300种疾病由胶原蛋白突变引起。目前，越来越多的报道显示了胶原蛋白和免疫系统的关系。但是目前的研究大多关注单个胶原蛋白对特异性免疫细胞的作用，而忽视了胶原蛋白网络作为一个高度交联的整体对组织免疫微环境的调节。秀丽线虫的胶原蛋白网络大多集中在与表皮上皮细胞相邻的外皮ECM中，与哺乳动物具有较高的同源性。在本课题中，我们拟充分利用线虫简单保守的固有免疫系统和基因敲除的易操作性等优点，系统全面地解析胶原蛋白网络对上皮细胞固有免疫的调控作用，揭示细胞外基质中的胶原蛋白在免疫应答调节中的普遍运作规律。并辅以哺乳动物模型验证在线虫模式中得到的研究成果，深入探索可影响固有免疫应答的胶原蛋白的运作规律和生理意义。

The collagens are an enormous family of extracellular matrix proteins that maintain the structure of various tissues. They play dominant roles in in cell adhesion, migration, and tissue remodeling during growth and in many pathologic states. However, their functions in regulating innate immunity remain largely undiscovered. Here we use C. elegans epidermis as the model to address this question. The adult C. elegans epidermis is a single-cell layered tissue covered with a collagen-rich cuticle exoskeleton. The C. elegans epidermal cells possess cell-autonomous defense machineries against invading pathogens or physical injury. When subjected to skin-penetrating fungal infection or physical injury, it activates specific innate defense through p38-MAPK or TGF-beta signaling cassettes and produces antimicrobial peptides (AMPs) such as nlp-29 and cnc-2. By inactivating 175 genes encoding C. elegans cuticle collagens one at a time, we pinpointed a small group of 6 collagens capable of triggering epidermal immune defense once absent. By screening most signaling molecules known to control AMP production, we found that the immune defense against collagen loss goes through MUP-4/STA-2 pathway, but not any other immune-related signaling pathways. By fully exploring the mechanisms underlying collagen-controlled epidermal innate immune response in C. elegans，we may help to uncover generic roles of collagens in regulation of innate immunity。 Results obtained from these studies may also provide mechanistic insights into the pathogenesis of inflammatory diseases involving the extracellular matrix.