Perinatal Thymic Innate Lymphocytes, Skin-homing, and Cutaneous Immune Homeostasis

与传统的T/B淋巴细胞不同，一组先天或先天类似的淋巴细胞，如 作为γδT细胞和先天淋巴样细胞，优先驻留在 它们在维持组织完整性的第一道防线中发挥着重要作用， 当调节失调时，也会导致组织炎症性疾病。理解 各种先天淋巴细胞的皮肤特异性定位和维持 调节是帮助设计针对特定先天淋巴细胞的策略的关键 用于治疗目的的人群。我们之前的研究发现，γδT细胞 在胎儿胸腺中产生的固有淋巴样细胞被编程为优先 表达皮肤归巢分子，包括趋化因子受体CCR10，用于其组织- 在皮肤中的特定分布。考虑到皮肤是最外层的上皮组织 在出生后接触到环境，我们认为内在的 胎儿胸腺固有淋巴细胞的程序化优先表达 皮肤归巢分子代表了一种以先天为目标的流行范例 淋巴细胞定位于特定的上皮组织，在围产期早期起到“边界”保护作用。 产后阶段。此外，胎儿起源的常驻γδT细胞和先天淋巴样细胞 显著促进成人皮肤免疫动态平衡的建立。 在这项资助中，我们将剖析调节皮肤的细胞和分子机制。 γδT和先天淋巴细胞不同亚群的定位。

Unlike conventional T/B lymphocytes, a group of innate or innate-like lymphocytes, such as γδ T cells and innate lymphoid cells, preferentially reside in epithelial tissues where they play important roles in the first line of defense to maintain the tissue integrity and, when dysregulated, also contribute to the tissue inflammatory diseases. Understanding how skin-specific localization and maintenance of the various innate lymphocytes are regulated is critical in helping to design the strategy targeting specific innate lymphocyte populations for therapeutic purposes. Our previous study have found that the γδT cells and innate lymphoid cells generated in the fetal thymus are programmed to preferentially express skin-homing molecules, including chemokine receptors CCR10, for their tissue- specific distribution in the skin. Considering the skin is the outmost epithelial tissue coming into contact with environments after the birth, we propose that the intrinsic programming of the fetal thymic innate lymphocytes for the preferential expression of skin-homing molecules represents a prevailing paradigm that targets the innate lymphocytes to the specific epithelial tissue for the “border” protection in the early peri- natal stage. In addition, the fetal originated resident γδT and innate lymphoid cells significantly contribute to the establishment of immune homeostasis in the skin of adults. In this grant, we will dissect cellular and molecular mechanisms regulating the skin localization of the different subsets of γδT and innate lymphocytes.