Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior
(2024) In Science 386(6721).- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2024-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science
- volume
- 386
- issue
- 6721
- article number
- eadi1025
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- pmid:39480923
- scopus:85208291368
- ISSN
- 1095-9203
- DOI
- 10.1126/science.adi1025
- language
- English
- LU publication?
- yes
- id
- 136cf6f8-fbe5-4654-927c-73871635d888
- date added to LUP
- 2025-01-09 11:12:20
- date last changed
- 2025-07-11 15:55:15
@article{136cf6f8-fbe5-4654-927c-73871635d888, abstract = {{<p>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.</p>}}, author = {{Barron, Jerika J. and Mroz, Nicholas M. and Taloma, Sunrae E. and Dahlgren, Madelene W. and Ortiz-Carpena, Jorge F. and Keefe, Matthew G. and Escoubas, Caroline C. and Dorman, Leah C. and Vainchtein, Ilia D. and Chiaranunt, Pailin and Kotas, Maya E. and Nowakowski, Tomasz J. and Bender, Kevin J. and Molofsky, Ari B. and Molofsky, Anna V.}}, issn = {{1095-9203}}, language = {{eng}}, number = {{6721}}, publisher = {{American Association for the Advancement of Science (AAAS)}}, series = {{Science}}, title = {{Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior}}, url = {{http://dx.doi.org/10.1126/science.adi1025}}, doi = {{10.1126/science.adi1025}}, volume = {{386}}, year = {{2024}}, }