Confined to cages within ultra-hygienic specific pathogen-free (SPF) facilities, laboratory mice are shielded from events commonly experienced by free-living mammals, such as environmental microorganisms. This absence of interaction with environmental variables significantly impacts the immune system's state, contributing to observed disparities when comparing laboratory mice with humans. While much attention has been given to the role of bacteria in this scene, recent research has highlighted the crucial role of nonbacterial agents, particularly fungi, in shaping host health and immunity. Our goal is to dissect how environmental fungi exert their effects on the immune landscape of the host. We are particularly interested in characterizing unique fungal-derived components or intermediates induced by fungi that directly control the lineage commitment of progenitors (the gut-bone marrow axis). Such knowledge can be critical to improve the utility of mouse models and to further our understanding of the role of environment in both homeostatic processes and in pathological conditions. In addition, we are fascinated by how early-life exposure reprograms the immune system and may influence the outcome of immune diseases later in life. By employing an interdisciplinary approach that leverages tools from high-dimensional flow cytometry, single-cell multimodal sequencing technology, microscopy, ex-vivo organoids, and in-vivo mouse model, we aim to uncover novel mechanisms that can be harnessed to modulate the heterogeneous differentiation of immune cell in response to various inflammatory diseases and cancer.