Stem cells (SCs) reside in a unique microenvironment or “niche” that is essential for their maintenance. Therefore, revealing the niche – SCs interactions is a key step needed for better understanding of SC regulation, function and their application in regenerative medicine. The cornea serves as an excellent model to study the SC niche, due to its transparency, accessibility and well-defined anatomy. Recently, we discovered two discrete SC populations and their corresponding niches that were termed the “outer” and “inner” limbus. While the outer limbus hosts quiescent SCs, the inner regime populates active SCs that maintain corneal epithelial homeostasis. Interestingly, distinct types of immune cells (e.g. T cells, dendritic cells, macrophages) were specifically identified in close proximity to outer and inner SCs. Moreover, immunodeficient mice and suppression of the immune system perturbed quiescence and delayed corneal regeneration, suggesting that immune cells may play a role as SC niche. However, the specific immune cell population and the regulatory mechanism between immune cells and corneal SC is yet to be elucidated. Here we propose to take advantage of the robustness of cornea as a SC model, that allows genetic SC and niche cell labeling, fate mapping and ablation in living mice to (i) characterize the sub-populations of immune niche cells in the limbus, (ii) explore the effect of their ablation on SCs, and finally, (iii) unravel the molecular mechanisms that underlie niche cell – SC interactions.