PT  - JOURNAL ARTICLE
AU  - Jerika J. Barron
AU  - Nicholas M. Mroz
AU  - Sunrae E. Taloma
AU  - Madelene W. Dahlgren
AU  - Jorge Ortiz-Carpena
AU  - Leah C. Dorman
AU  - Ilia D. Vainchtein
AU  - Caroline C. Escoubas
AU  - Ari B. Molofsky
AU  - Anna V. Molofsky
TI  - Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior
AID  - 10.1101/2023.03.16.532850
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.03.16.532850
4099  - http://biorxiv.org/content/early/2023/03/17/2023.03.16.532850.short
4100  - http://biorxiv.org/content/early/2023/03/17/2023.03.16.532850.full
AB  - The innate immune system plays essential roles in brain synaptic development, and immune dysregulation is implicated in neurodevelopmental diseases. Here we show that a subset of innate lymphocytes (group 2 innate lymphoid cells, ILC2s) is required for cortical inhibitory synapse maturation and adult social behavior. ILC2s expanded in the developing meninges and produced a surge of their canonical cytokine Interleukin-13 (IL-13) between postnatal days 5-15. Loss of ILC2s decreased cortical inhibitory synapse numbers in the postnatal period where as ILC2 transplant was sufficient to increase inhibitory synapse numbers. Deletion of the IL-4/IL-13 receptor (Il4ra) from inhibitory neurons phenocopied the reduction inhibitory synapses. Both ILC2 deficient and neuronal Il4ra deficient animals had similar and selective impairments in adult social behavior. These data define a type 2 immune circuit in early life that shapes adult brain function.One sentence summary Type 2 innate lymphoid cells and Interleukin-13 promote inhibitory synapse development.Competing Interest StatementThe authors have declared no competing interest.