Immune cells that originate in the meninges have an increasingly appreciated role in brain development and homeostasis. Most studies of this role have focused on meningeal T cells; now, writing in Science, Barron et al. show that innate lymphoid cells (ILCs) regulate the development of inhibitory neurons in the mouse prefrontal cortex. Throughout postnatal brain development, meningeal innate lymphocytes outnumbered meningeal adaptive lymphocytes, with the number of group 2 ILCs (ILC2s) and their production of the cytokines IL-5 and IL-13 peaking in postnatal weeks 2 to 3. Ablation of ILC2s or IL-13 receptor subunits during development led to the mice having fewer inhibitory synapses in cortex on postnatal day 15, and intracerebroventricular infusion of ILC2 or IL-13 increased the number of these synapses; excitatory synapses were unaffected by these manipulations. Although IL-13 receptor subunits are expressed by microglia, myeloid cells and neurons, only their deletion in inhibitory interneurons reduced inhibitory synapse numbers. Compared to control mice, mice lacking ILC2s or the IL-13 receptor subunit IL4RA spent less time interacting with another mouse in early adulthood, but they showed normal behaviour on other tests. These findings add to our understanding of the importance of meningeal immune cells.

Original reference: Science 386, eadi1025 (2024)