Laboratory for Innate Immune Systems

Over the past year, our laboratory has investigated how innate lymphoid cells (ILCs) orchestrate tissue homeostasis and disease progression through dynamic interactions with stromal, epithelial, and metabolic systems. 

In the context of endometriosis, a chronic inflammatory disorder of reproductive-age women, we identified group 2 innate lymphoid cells (ILC2s) as key drivers of lesion growth. Using murine models, we demonstrated that immune cells within endometriotic lesions originate from host tissues rather than transplanted endometrial fragments. We further uncovered a pathogenic feedback loop in which Sca-1⁺ fibroblasts serve as a dominant source of IL-33, inducing amphiregulin (AREG) production by infiltrating ILC2s. ILC2-derived AREG, in turn, stimulates fibroblast proliferation, promoting lesion enlargement. These findings reveal a previously unrecognized ILC2–fibroblast axis and highlight IL-33–AREG signaling as a potential therapeutic target in endometriosis. 

In the skin, we uncovered a mechanosensory immune circuit that maintains epithelial turnover under physiological mechanical stress. Mild perturbation of the stratum corneum induces keratinocyte-derived extracellular ATP, which activates skin-resident ILC1s via the high-affinity receptor P2RX1, leading to AREG production. This pathway enhances basal cell proliferation, differentiation, and stratum corneum shedding, thereby facilitating the clearance of microbes and allergens. Disruption of this axis compromises barrier resilience and promotes atopic-like inflammation. 

We also explored the role of ILC3s in metabolic regulation, demonstrating that feeding-induced activation of intestinal ILC3s drives VEGF-A–dependent modulation of capillary permeability, enabling portal lipid transport. This pathway links immune sensing to systemic lipid metabolism, obesity resistance, and fasting-induced ketogenesis. 

Finally, using a cecal resection model of ulcerative colitis, we identified an appendix–microbiota–tuft cell axis in which microbiota-derived oxidized lipids induce tuft cell hyperplasia, IL-25–ILC2 activation, and IL-13–dependent mucus production, collectively strengthening epithelial barrier function and protecting against colitis. 

Together, our work reveals fundamental principles by which ILCs integrate mechanical, microbial, and metabolic cues to regulate tissue health and disease.