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

与传统的T/B淋巴细胞不同，一组先天或先天样淋巴细胞，如 如γδ T细胞和先天性淋巴样细胞，优先存在于上皮组织中， 它们在维持组织完整性的第一道防线中起重要作用， 当失调时，也会导致组织炎性疾病。理解 各种先天淋巴细胞的皮肤特异性定位和维持是如何 调节在帮助设计靶向特定先天淋巴细胞的策略中至关重要。 人群用于治疗目的。我们以前的研究发现，γδT细胞 胎儿胸腺中产生的先天性淋巴细胞被编程为优先 表达皮肤归巢分子，包括趋化因子受体CCR 10，为他们的组织- 在皮肤中的具体分布。考虑到皮肤是最外层的上皮组织 出生后与环境接触，我们认为， 胎儿胸腺先天淋巴细胞的程序化，用于优先表达 皮肤归巢分子代表了一种流行的范式， 淋巴细胞到特定的上皮组织的“边界”的保护，在早期的癌症， 纳塔尔阶段此外，胎儿起源的常驻γδT和先天性淋巴细胞 显著有助于在成人皮肤中建立免疫稳态。 在这份资助中，我们将剖析调节皮肤的细胞和分子机制 γδT和先天性淋巴细胞的不同亚群的定位。

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.