# Resolution of neutrophil response for effective T cell functions and tissue repair

> **NIH NIH P01** · UNIVERSITY OF ROCHESTER · 2021 · $385,336

## Abstract

PROJECT SUMMARY/ABSTRACT – PROJECT 1
Migration of neutrophils to sites of tissue infection is vital for pathogen clearance and, thus, host survival.
Importantly, once they complete their action, infiltrated neutrophils during the early infection phase should
quickly initiate spontaneous apoptosis. A delayed neutrophil resolution is often associated with widespread
tissue damage, organ failure, and ultimately death in severely infected patients. Therefore, the presence of
unresolved neutrophil response during infection has long been believed to be detrimental, making it more
difficult for patients to recover. Although growing evidence now suggests that neutrophils not only contribute to
the tissue damage, but also orchestrate T cell functions and tissue repair, it has been challenging to clearly
differentiate host-protective roles of neutrophils from their damaging inflammatory functions because most of
the studies used over-activated or inappropriate inflammatory responses, which fail to restore tissue
homeostasis. Therefore, the contribution of neutrophils to the host immune response and tissue repair may not
be properly evaluated in these models. We undertook this study to address critical knowledge gaps regarding
the function and fate of neutrophils during the infection. Through several lines of evidence from our preliminary
study using a fully recovering mouse influenza infection model, we propose novel functions of neutrophil that
can actively promote tissue healing and the resolution of inflammation. We discovered that apoptotic
neutrophils actively engage with the proliferation and survival of other surrounding cells (e.g., epithelial cells
and macrophages). This mitogenic and pro-survival effect of apoptotic neutrophils was mainly mediated by the
secretion of epidermal growth factor (EGF). Moreover, live intravital multiphoton microscopy (IV-MPM) of our
newly generated Ly6GCre/ROSAtdTomato/Csf1r-EGFP mice revealed a striking motility pattern of neutrophils and
their phagocytes during the resolution phase within the infected airway, which may represent additional
beneficial functions of neutrophils in protecting the host against infections. We hypothesize that resolution of
neutrophil response during influenza infection is not merely a passive termination of the early neutrophil
infiltrates but rather an active biochemical and cellular process to establish effective T cell immune responses
while enabling tissues to repair and return to normal function. We will test the hypothesis that (1) apoptotic
neutrophils promote tissue repair and (2) neutrophils control their own clearance. We will also determine (3)
whether neutrophil resolution regulates T cell functions and memory formation. Given the important immune-
modulatory properties of neutrophils, understanding of novel functions of neutrophil during the resolution of
inflammation could be harnessed to combat infection and chronic inflammatory conditions.

## Key facts

- **NIH application ID:** 10241368
- **Project number:** 5P01AI102851-08
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Minsoo Kim
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,336
- **Award type:** 5
- **Project period:** 2014-06-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241368

## Citation

> US National Institutes of Health, RePORTER application 10241368, Resolution of neutrophil response for effective T cell functions and tissue repair (5P01AI102851-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241368. Licensed CC0.

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