# Determining the role of type I interferons in ultraviolet-B light induced keratinocyte death

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $37,921

## Abstract

PROJECT SUMMARY/ABSTRACT
Lupus erythematosus is a chronic, debilitating autoimmune disease that disproportionately affects women of
childbearing age and has been found to be among the leadings causes of death in this population. The systemic
form of the disease, systemic lupus erythematosus (SLE), has heterogeneous clinical manifestations that can
affect nearly all major organs of the body. When there is skin involvement, the disease is grouped under the
category of cutaneous lupus erythematosus (CLE). CLE can occur on its own or in combination with systemic
disease with up to 70% of SLE patients experiencing cutaneous involvement. Both SLE and CLE are
characterized by increased sensitivity to ultraviolet (UV) light. UV light can trigger cutaneous and systemic
disease flares that severely diminish patient quality of life and carry significant economic burdens. As the
mechanisms driving these responses are not understood, few treatment options exist with prevention largely
based on sun avoidance and sunscreen use. Type I interferons (IFNs), a group of cytokines generally produced
in response to viral infection, are chronically overexpressed in lupus patients with circulating levels correlating
with cutaneous disease activity. Type I IFNs regulate expression of several genes that may play a role in
photosensitivity including pro-apoptotic Xaf1 and chemokines that promote natural killer (NK) cell recruitment
and activation. The Kahlenberg laboratory previously observed that type I interferons (IFNs) are increased at
baseline in SLE keratinocytes (KCs) and promote cell death after UV exposure. However, the specific pathways
regulated by type I IFNs that enhance UV-driven KC death are not known. This proposal will test the hypothesis
that chronic overexpression of type I IFNs in lupus skin primes keratinocytes for increased UVB-induced
extrinsic apoptosis through upregulated XAF1 expression and enhanced recruitment and activation of
cytotoxic NK cells. This hypothesis will be tested through three specific aims: (1) Examine activation of extrinsic
vs. intrinsic apoptosis in type I IFN-primed skin following UVB exposure, (2) Determine the role of XAF1 in type
I IFN-driven KC apoptosis, and (3) Identify the role of NK cells in type I IFN-driven KC apoptosis. To accomplish
these specific aims, human cell lines and genetically engineered mouse models will be used to perform in vitro
and in vivo experiments investigating cell signaling and genetic regulation of type I IFN-primed KCs exposed to
UV light and to determine how this influences NK cells that are recruited into the skin. The results from these
studies will establish the impacts of type I IFN overproduction in lupus skin in the context of photosensitivity with
the overall future goal of identifying targets for new treatment options for patients whose disease is flared by the
sun. This project will serve as a crucial mechanism through which the applicant will further expand her core skills
in experi...

## Key facts

- **NIH application ID:** 10065202
- **Project number:** 1F31AR077988-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Shannon Loftus
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,921
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065202

## Citation

> US National Institutes of Health, RePORTER application 10065202, Determining the role of type I interferons in ultraviolet-B light induced keratinocyte death (1F31AR077988-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10065202. Licensed CC0.

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