Unlike conventional T/B lymphocytes, a group of innate or innate-like lymphocytes, such as ?? 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 ??T 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 ??T 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 ??T and innate lymphocytes.