# Defining lymphocyte-microglia crosstalk during cortical synapse development

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $38,080

## Abstract

PROJECT SUMMARY / ABSTRACT
There is ample evidence of immune dysfunction in neurodevelopmental and psychiatric disorders and immune
signaling is known to impact synapse development. Microglia, the tissue-resident macrophages of the brain, are
key conduits of these immune signals. They can both promote synapse formation and prune away synapses,
which has been shown to be regulated by immune molecules in physiologic development. However, the
discovery of many other immune cells in the meningeal compartment surrounding the brain at rest raises the
question of whether these cells play a physiologic role in the central nervous system, perhaps via communication
with microglia. Lymphocytes and lymphocyte-derived cytokines have been shown to promote normal cognition
and behavior in adult mice, but their physiological roles, particularly during development, are largely unknown.
Our group identified abundant lymphocytes in the brain meninges throughout postnatal development. We also
find that microglia are competent to respond to lymphocyte-derived cytokines, particularly Interleukin-13 (IL-13),
a canonical type 2 cytokine. IL-13 induces transcription of genes in microglia consistent with cell migration, and
cell-cell and extracellular matrix (ECM) adhesion, which may increase their synapse remodeling functions. The
predominant producers of IL-13 under homeostatic conditions are type 2 innate lymphoid cells (ILC2s), which
we find present in the developing meninges and poised for cytokine production during a critical period of synapse
formation and pruning. Loss of ILC2s leads to altered inhibitory and excitatory synapse numbers in the
developing cortex. Based on these data, the central hypothesis of this work is that ILC2s promote post-natal
synapse development via IL-13 signaling to microglia and regulation of their synaptic remodeling functions. To
test this hypothesis, this proposal will determine the requirement for ILC2s and IL-13 in promoting cortical
synapse function (Aim 1) and define the direct impact of IL-13 signaling on microglia synapse remodeling
function, namely engulfment (Aim 2). Genetic mouse models will be used for targeted deletion of ILC2s and of
the IL-13 receptor from microglia. This work will employ slice electrophysiology to determine synaptic function
as well as immunohistochemistry and high-resolution imaging to examine microglial engulfment and synapse
density. This work leverages the expertise and tools of neurodevelopmental glial biologists and innate
immunologists to address this important question in neuroimmunology. Successful completion of these aims will
reveal a novel role for ILC2-microglia communication in regulating neurodevelopment. Elucidating the impact of
lymphocytes and their cytokines on physiologic brain development is significant for understanding how
dysregulated immune responses may contribute to neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10400575
- **Project number:** 5F31MH122207-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jerika Janet Barron
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,080
- **Award type:** 5
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400575

## Citation

> US National Institutes of Health, RePORTER application 10400575, Defining lymphocyte-microglia crosstalk during cortical synapse development (5F31MH122207-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10400575. Licensed CC0.

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