The interaction of innate lymphocytes and dendritic cells regulates an intestinal precursor niche

肠道的免疫系统是一个非常未知的领域。然而，它类似于生物体中最有趣的系统之一，因为它能够在炎症性食物和细菌抗原的持续挑战下保持抗炎状态。肠道内的先天免疫系统能够迅速对这种微妙平衡的变化做出反应，并通过操纵先天免疫系统其他细胞的发育和募集来防止炎症结果。在这项研究计划中，我们将确定调节骨髓外先天免疫细胞发育（淋巴细胞和骨髓细胞）的细胞和分子线索。淋巴组织诱导细胞、自然杀伤细胞、树突状细胞和巨噬细胞是肠道先天免疫系统的主要成分。异种共生，一种连接两只实验动物血液的显微外科方法，将使我们能够回答先天免疫细胞是否调节其他先天免疫细胞的募集和发育的问题。此外，我们将对肠道先天免疫细胞产生的生长因子进行详细评估，这些生长因子可能操纵淋巴和骨髓的形成。总的来说，我们的研究将为先天免疫细胞是否能够在骨髓以外的器官中发育提供实验证据。这些结果将把肠道、胸腺和骨髓作为免疫细胞发育的地方。

The immune system of the intestine is a vastly unknown area. However, it resembles one of the most interesting systems in the organism, as it is able to maintain an anti-inflammatory state though constant challenges by inflammatory food-prone and bacterial antigens. The innate immune system inside the intestine is able to quickly react to changes within this delicate balance and prevent an inflammatory outcome through manipulation the development and recruitment of other cells of the innate immune system. Within this research proposal, we are going to identify the cellular and molecular cues that regulate the development (lymphopoiesis and myelopoiesis) of innate immune cells outside the bone marrow. Lymphoid tissue inducer cells, natural killer cells, dendritic cells and macrophages are the main compounds of the intestinal innate immune system. Parabiosis, a microsurgical method to connect the bloodstream of two experimental animals will allow us to answer the question whether innate immune cells regulate the recruitment and development of other innate immune cells. Furthermore, we will perform a detailed assessment of growth factors produced by innate immune cells of the intestine that might manipulate lympho- and myelopoiesis. Collectively, our study will provide experimental evidence of whether innate immune cells are able to develop in organs others than the bone marrow. These results would place the intestine, beside the thymus and the bone marrow as place for immune cell development.