# IL22 signaling in epilepsy

> **NIH NIH R01** · ALBANY MEDICAL COLLEGE · 2021 · $408,320

## Abstract

Epileptogenesis is a pathological process that transforms a normal brain into an epileptic brain, typically
initiated by genetic mutations and neurological insults such as status epilepticus (SE). There is an unmet need
to understand epileptogenesis because it remains nearly unpreventable. Brain inflammation triggered by
neuronal injury is increasingly recognized as a contributor to epileptogenesis. Microglia, generally considered
as resident macrophages, are highly proliferated and activated in response to epileptogenic insults and thought
to play a primary role. Besides resident microglia, other immune cells in the peripheral system and CNS
lymphatic system also infiltrate the CNS compartment and likely contribute to epileptogenesis. It remains to be
understood how CNS resident and non-resident immune cells interact in response to epileptogenic insults and
how the injury-triggered changes in the immune network impinge on non-immune cells such as astrocytes and
neurons, thereby contributing to epileptogenesis. This proposal is built on our observation that IL22Rα1 is
strongly up-regulated in astrocytes in the pilocarpine model of temporal lobe epilepsy. This induction depends
on brain inflammation. Moreover, the induction of IL22Rα1 is critically involved in astrogliosis, an excessive
proliferation and activation of astrocytes frequently seen in epileptic brains. These findings lead to our central
hypothesis, that up-regulation of IL22/IL22Rα1 signaling promotes astrocyte proliferation, which in turn
contributes to epileptogenesis. Three specific aims are proposed to test our hypothesis. Aim 1 will determine
how IL22Rα1 expression is up-regulated in astrocytes. Aim 2 will elucidate how IL22-producing immune cells
are recruited into the CNS compartment. Aim 3 will determine if blocking IL22 signaling attenuates astrogliosis
and modifies the process of epileptogenesis. Our study will not only improve our understanding how IL22
signaling regulates epileptogenesis, but could also identify druggable targets to prevent epileptogenesis.

## Key facts

- **NIH application ID:** 10140433
- **Project number:** 5R01NS112713-02
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** Yunfei Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $408,320
- **Award type:** 5
- **Project period:** 2020-04-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140433

## Citation

> US National Institutes of Health, RePORTER application 10140433, IL22 signaling in epilepsy (5R01NS112713-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10140433. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*