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

View ORCID ProfileJerika J. Barron, Nicholas M. Mroz, Sunrae E. Taloma, Madelene W. Dahlgren, Jorge Ortiz-Carpena, Leah C. Dorman, Ilia D. Vainchtein, Caroline C. Escoubas, Ari B. Molofsky, View ORCID ProfileAnna V. Molofsky
doi: https://doi.org/10.1101/2023.03.16.532850
Jerika J. Barron
1Departments of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA
2Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA
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  • ORCID record for Jerika J. Barron
Nicholas M. Mroz
2Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA
4Department of Laboratory Medicine. University of California, San Francisco, San Francisco, CA
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Sunrae E. Taloma
1Departments of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA
3Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA
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Madelene W. Dahlgren
4Department of Laboratory Medicine. University of California, San Francisco, San Francisco, CA
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Jorge Ortiz-Carpena
4Department of Laboratory Medicine. University of California, San Francisco, San Francisco, CA
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Leah C. Dorman
1Departments of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA
3Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA
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Ilia D. Vainchtein
1Departments of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA
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Caroline C. Escoubas
1Departments of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA
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Ari B. Molofsky
4Department of Laboratory Medicine. University of California, San Francisco, San Francisco, CA
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  • For correspondence: anna.molofsky@ucsf.edu ari.molofsky@ucsf.edu
Anna V. Molofsky
1Departments of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA
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  • ORCID record for Anna V. Molofsky
  • For correspondence: anna.molofsky@ucsf.edu ari.molofsky@ucsf.edu
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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 summary Type 2 innate lymphoid cells and Interleukin-13 promote inhibitory synapse development.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 17, 2023.
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Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior
Jerika J. Barron, Nicholas M. Mroz, Sunrae E. Taloma, Madelene W. Dahlgren, Jorge Ortiz-Carpena, Leah C. Dorman, Ilia D. Vainchtein, Caroline C. Escoubas, Ari B. Molofsky, Anna V. Molofsky
bioRxiv 2023.03.16.532850; doi: https://doi.org/10.1101/2023.03.16.532850
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Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior
Jerika J. Barron, Nicholas M. Mroz, Sunrae E. Taloma, Madelene W. Dahlgren, Jorge Ortiz-Carpena, Leah C. Dorman, Ilia D. Vainchtein, Caroline C. Escoubas, Ari B. Molofsky, Anna V. Molofsky
bioRxiv 2023.03.16.532850; doi: https://doi.org/10.1101/2023.03.16.532850

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