Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior
The innate immune system shapes brain development and is implicated in neurodevelopmental diseases. It is critical to define the relevant immune cells and signals and their impact on brain circuits. In this work, we found that group 2 innate lymphoid cells (ILC2s) and their cytokine interleukin-13 (IL-13) signaled directly to inhibitory interneurons to increase inhibitory synapse density in the developing mouse brain. ILC2s expanded and produced IL-13 in the developing brain meninges. Loss of ILC2s or IL-13 signaling to interneurons decreased inhibitory, but not excitatory, cortical synapses. Conversely, ILC2s and IL-13 were sufficient to increase inhibitory synapses. Loss of this signaling pathway led to selective impairments in social interaction. These data define a type 2 neuroimmune circuit in early life that shapes inhibitory synapse development and behavior.
Authors
- Caroline C. Escoubas (ORCID: https://orcid.org/0000-0001-7113-1532)
- Nicholas M. Mroz
- Jerika J. Barron (ORCID: https://orcid.org/0000-0002-8983-3126)
- Tomasz J. Nowakowski (ORCID: https://orcid.org/0000-0003-2345-4964)
- Leah C. Dorman (ORCID: https://orcid.org/0000-0002-5511-887X)
- Pailin Chiaranunt (ORCID: https://orcid.org/0000-0001-8753-1469)
- Ilia D. Vainchtein (ORCID: https://orcid.org/0000-0003-3190-8524)
- Madelene W. Dahlgren (ORCID: https://orcid.org/0000-0002-8640-0157)
- Kevin J. Bender (ORCID: https://orcid.org/0000-0001-7084-1532)
- Jorge F. Ortiz-Carpena (ORCID: https://orcid.org/0000-0002-7727-9674)
- Sunrae E. Taloma (ORCID: https://orcid.org/0000-0002-7210-8614)
- Ari B. Molofsky (ORCID: https://orcid.org/0000-0003-0764-3175)
- Matthew G. Keefe (ORCID: https://orcid.org/0000-0002-2477-2975)
- Anna V. Molofsky
- Maya E. Kotas (ORCID: https://orcid.org/0000-0002-8102-6346)
Institutions
- University of California, San Francisco (US)
- Lund University (SE)
- University of California System (US)
- Chan Zuckerberg Initiative (United States) (US)
Publication Details
- Journal
- Science
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1126/science.adi1025
- Citations
- 43
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 10.34
Funders
- National Science Foundation
- Vetenskapsrådet
- National Institutes of Health
- University of California, Davis
- University of California, San Francisco
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- National Institute of Allergy and Infectious Diseases
- National Institute of Neurological Disorders and Stroke