Characterizing lymphocyte-glia crosstalk in the developing brain Jerika Barron1,2, Madelene Dahlgren3, Jorge Ortiz-Carpena3, Ari B. Molofsky3, Anna V. Molofsky1 1Department of Psychiatry, 2Biomedical Sciences Graduate Program, 3Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA
Immune signaling is increasingly recognized for its role in homeostasis and development. Consistent with this, its dysregulation has been implicated in a number of neurodevelopmental and psychiatric disorders, including autism and schizophrenia. Lymphocytes and lymphocyte-derived cytokines have been shown to promote normal cognition and behavior and are involved in reparative responses after injury. The discovery of immune cells in the meningeal compartment surrounding the brain at rest raises the question of whether these cells may be playing a physiologic role in development. Lymphocytes such as type 2 innate lymphoid cells (ILC2s), which are important for homeostasis and repair in other tissues, in addition to their role in barrier immunity, may promote similar functions in the developing brain. Key to their function is their ability to produce cytokines at rest and communicate with their environment. In this work, we characterized the composition of the mouse meningeal immune compartment throughout post-natal development. We observed an increase in ILC2s during this time and found that they were competent to produce the canonical type 2 cytokine IL-13. We also found that exogenous IL-13 leads to alterations in microglia morphology and gene expression, suggesting that microglia are able to respond to IL-13 signals during development. Future studies will address the requirement of ILC2s and other meningeal lymphocytes for normal brain development and in models of neurodevelopmental disorders.
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