Systemic analysis of the molecular mechanisms of leukocyte entry into the pancreas

淋巴细胞，也被称为白血球，通过在全身循环来保护身体免受微生物、病毒和癌症的侵袭。除淋巴组织(脾、淋巴结、骨髓等)外，包括胰腺在内的所有其他组织中都可发现少量淋巴细胞。淋巴细胞进入大脑、眼睛、肌肉或胰腺等组织受特定蛋白质和过程的调节。淋巴细胞异常或促进进入这些非淋巴组织可导致严重的免疫病理。值得注意的是，在1型和2型糖尿病中都发现了胰腺中的淋巴细胞浸润。阻止免疫细胞进入胰腺肯定会为糖尿病患者提供治疗益处。我们的总体目标是确定允许正常和异常淋巴细胞在胰腺中渗透的蛋白质。我们将使用两种互补的非靶向方法来确定促进淋巴细胞进入胰腺组织的关键途径。首先，通过一种新的分子生物学方法，命名为ProCode，我们将测试200多种蛋白质在抑制或促进淋巴细胞进入胰腺中的作用。其次，我们将从合作十字中筛选200多个品系的小鼠，并确定其中哪些小鼠的胰腺中存在更多或更少的淋巴细胞。正如协作交叉小鼠的基因组所知，这种无偏见的方法将揭示影响淋巴细胞进入胰腺的基因。总之，这些互补的方法将揭开特定的分子途径，这些途径需要有针对性地防止淋巴细胞进入胰腺组织。

Lymphocytes, also known as white blood cells, defend the body against microbes, viruses and cancer by circulating throughout the body. Aside from lymphoid tissues (spleen, lymph nodes, bone marrow, etc), a small number of lymphocytes can be found in all other tissues, including the pancreas. Entry of lymphocytes in tissues such as the brain, the eyes, the muscles or the pancreas is regulated by specific proteins and processes. Aberrant or facilitated entry of lymphocytes into these non-lymphoid tissues can lead to severe immune pathologies. Notably, lymphocyte infiltrates in the pancreas have been documented in both type 1 and type 2 diabetes. Blocking immune cell entry in the pancreas would certainly provide therapeutic benefit to diabetes patients. Our overall objective is to identify the proteins that allow both normal and aberrant lymphocyte infiltration in the pancreas. We will use two complementary non-targeted approach to identify key pathways facilitating lymphocyte entry into pancreatic tissue. First, by a novel molecular biology approach, namedly ProCode, we will test the role of over 200 proteins in inhibiting or facilitating lymphocyte entry in the pancreas. Second, we will screen over 200 strains of mice from the Collaborative Cross and determine which of these mice present with more or less lymphocytes in the pancreas. As the genome of the Collaborative Cross mice is known, this unbiased approach will reveal genes that influence lymphocyte entry in the pancreas. Altogether, these complementary approaches will unravel the specific molecular pathways that need to be targeted to prevent lymphocyte entry in pancreatic tissue.