# Natural Killer Cell Regulation of Skin Inflammation

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $480,292

## Abstract

PROJECT SUMMARY
Characterized by chronic skin inflammation, atopic dermatitis (AD) is the most common chronic illness of
childhood and is often a lifelong disease. Numerous immune cell types have been implicated in AD
pathogenesis, including mast cells, basophils, and T helper type 2 (Th2) cells. Recent studies by the Kim Lab
identified group 2 innate lymphoid cells (ILC2s) as critical contributors to development of AD/AD-like disease
through production of the type 2 cytokines IL-4 and IL-13. Indeed, blockade of the IL-4 and IL-13 receptor (IL-
4R) has emerged as the first FDA-approved targeted therapy for moderate-to-severe AD. Despite this major
advance, <40% of AD patients in phase III clinical trials met the primary endpoint in terms of disease
improvement. Development of new AD therapies is hindered by an incomplete understanding of the immune
cell types that regulate the disease beyond type 2 immune cells. There is an urgent need to correct this
knowledge gap to develop effective therapies for AD. Our long-term goal is to target immune regulators of AD
to develop new therapies. The overall objective of our proposal is to identify the immune cell types and effector
mechanisms that regulate AD-like disease. Our central hypothesis is that circulating natural killer (NK) cells are
major regulators of type 2 inflammation in the skin that can be harnessed to treat AD. NK cells have been
implicated in antitumor and antiviral immunity through their production of cytolytic proteins as well as interferon-
gamma (IFN-). Recent studies suggest that NK cells may negatively regulate ILC2s in the lung, but the role of
NK cells in the skin and AD remains unclear. In preliminary studies, we revealed that mouse NK cells critically
suppress skin ILC2 responses in vivo. In humans, we identified that circulating blood NK cells are markedly
deficient in moderate-to-severe AD and increase with disease resolution. The rationale for this proposal is that
once it is understood how NK cells influence AD pathogenesis, these mechanisms can be harnessed to create
effective and novel AD therapies.

## Key facts

- **NIH application ID:** 10119958
- **Project number:** 1R01AR077007-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Brian Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $480,292
- **Award type:** 1
- **Project period:** 2021-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119958

## Citation

> US National Institutes of Health, RePORTER application 10119958, Natural Killer Cell Regulation of Skin Inflammation (1R01AR077007-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10119958. Licensed CC0.

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