Neuro-Immune Regulome Unit

The Neuro-Immune Regulome Unit (NIRU) aims to understand the mechanisms that precisely regulate gene expression in lymphoid cells through multidisciplinary genomic approaches. Lymphoid cells communicate the perturbation of homeostasis by production of cytokines, dysregulation of which results in neural and ocular inflammation in many disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, uveitis and age-related macular degeneration. Understanding the basic pathophysiology of cytokine production in these contexts – for example, their source and regulation – represents a promising path for the development of more specific and efficacious therapies.

Precise orchestration of gene regulation in lymphocytes is mediated by networks of signaling molecules, transcription factors, and genomic regulatory regions, which in sum is termed regulomes. Previously, we have identified lineage-specific regulomes in tissue-resident innate and adaptive lymphocytes in both homeostatic and activated states by integrating cutting-edge techniques and computational approaches (Shih et al., Cell, 2016; Harrison et al., Science, 2018; Kobayashi et al., Cell, 2019; Nagashima et al., Immunity, 2019). We now are focusing on two key biological questions 1) How do distinct stimuli regulate cytokines in a context-specific manner? 2) How cytokines contribute to the progression of neurodegeneration, such as Alzheimer’s disease and age-related macular degeneration? By analyzing lymphocyte regulomes with distinct genetic background in human and engineered mice, we aim to further our understanding of molecular mechanisms that contribute to aging and neurodegenerative diseases.