# T cell roles in regeneration across nerve graft alternatives

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $370,125

## Abstract

PROJECT SUMMARY / ABSTRACT
Achieving meaningful restoration of function after nerve defects are repaired is still a major unmet clinical
challenge. Due to disadvantages of nerve autografting, nerve graft alternatives are being increasingly used and
desired for defect repair. But clinically, these alternatives do not promote consistent regeneration and recovery.
Furthermore, we still do not understand what factors are critical to promote consistent nerve regeneration
across repaired nerve defects that yields meaningful recovery. To understand mechanisms that promote nerve
regeneration across nerve graft alternatives and functional recovery, we have used the clinically-relevant nerve
graft alternative, acellular nerve allografts (ANAs), as a model. Recently, we determined a critical role for the
adaptive immune system during regeneration across ANAs. We found that nerve regeneration across short
ANAs repairing nerve defects in wild-type (WT) mice was robust, while regeneration across ANAs in T and B
cell deficient mice (RAG1KO) was impaired. The ANAs within RAG1KO mice contained reduced Type 2
cytokine (i.e. IL-4) levels compared to WT ANAs. IL-4 expression was regulated via CD4 T cells and
eosinophils. And in IL-4KO mice, regeneration across ANAs was also impaired. Overall, we have evidence that
T cells contribute to nerve regeneration across ANAs through regulation of IL-4 expression within ANAs.
Therefore, in our aims we will (1) dissect which adaptive immune cells, including CD4 T cells, affect nerve
regeneration across ANAs, (2) identify how IL-4 expression is regulated within ANAs, and (3) determine the
targets of IL-4 that promote nerve regeneration across ANAs. In summary, our studies will reveal the cells of
the adaptive immune system contributing to nerve regeneration and demonstrate how IL-4 signaling promotes
regeneration across nerve graft alternatives.

## Key facts

- **NIH application ID:** 10322193
- **Project number:** 5R01NS115960-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Matthew D. Wood
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,125
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322193

## Citation

> US National Institutes of Health, RePORTER application 10322193, T cell roles in regeneration across nerve graft alternatives (5R01NS115960-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10322193. Licensed CC0.

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