Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior

Barron, J. J.; Mroz, N. M.; Taloma, S. E.; Dahlgren, M. W.; Ortiz-Carpena, J. F.; Dorman, L. C.; Vainchtein, I. D.; Escoubas, C. C.; Molofsky, A. B.; Molofsky, A. V.

doi:10.1101/2023.03.16.532850

bioRxiv · 10.1101/2023.03.16.532850

Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior

Barron, J. J.·Mroz, N. M.·Taloma, S. E.·Dahlgren, M. W.·Ortiz-Carpena, J. F.·Dorman, L. C.·Vainchtein, I. D.·Escoubas, C. C.·Molofsky, A. B.·Molofsky, A. V.

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Abstract

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 summaryType 2 innate lymphoid cells and Interleukin-13 promote inhibitory synapse development.

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Barron, J. J., Mroz, N. M., Taloma, S. E., Dahlgren, M. W., Ortiz-Carpena, J. F., Dorman, L. C., Vainchtein, I. D., Escoubas, C. C., Molofsky, A. B., Molofsky, A. V.. 2023-03-17. Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior. https://doi.org/10.1101/2023.03.16.532850

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