# Extracellular vesicles as a novel mediator for ultraviolet-B light induced photoaging and skin inflammation.

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2024 · —

## Abstract

Ultraviolet B (UVB) irradiation causes skin inflammation, photodamage, and photoaging, all major
medical problems for Armed Forces personnel and veterans. Because UVB is absorbed mostly by
the epidermis, with just 10% reaching the dermis, we seek to investigate likely signals from
epidermis to mediate inflammation and damage in the dermis in response to UVB. Extracellular
vesicles (EVs), which are small lipid bilayer membrane structures released by many cells, carry
lipids, proteins, and nucleic acids to mediate cell-cell communication. Data from us and others
indicate that UVB irradiation of keratinocytes (KCs) triggers the release of biologically active EVs.
Our preliminary data suggest that these UVB-induced KC-derived EVs (KC-EVs) activate several
key pro-inflammatory pathways in dermal cells, including the stimulator of interferon genes
(STING), the NLRP3 inflammasome, and NF-KB. Our central hypothesis is that UVB provokes
KCs in the epidermis to release biologically active EVs that then leave the epidermis to act on
dermal fibroblasts, immune cells in the dermis, and even systemically, to mediate photoaging and
other harms. There are three Aims. Aim 1. To characterize KC-EVs induced by UVB irradiation
and the immune cells they act upon in vivo in the dermis and in vitro. Experimental approaches
include UVB-irradiation of mice followed by isolation and characterization of KC-EVs from dermis
(1a); use in vivo of GW4869, an agent that blocks EV generation, to determine which immune cell
types are no longer recruited by UVB to dermis, or are recruited but not activated (1b); and
identification of target immune cell types that respond to KC-EVs in vitro (1c) and in vivo (1d),
including after intradermal injection of UVB- induced KC-EVs into mice. Aim 2. To characterize
molecular mechanisms by which KC-EVs mediate UVB-induced dermal inflammation. We will test
the roles of STING, the inflammasome, and NF-KB (2a) using experimental systems in vivo and in
vitro from Aim 1. We will also test the roles of specific biologically active molecules carried by KC-
EVs, such as dsDNA, peroxidized lipids known to function as danger signals, and specific
proteins, such as integrins (2b). Aim 3. To assess potential therapeutic strategies that ameliorate
KC-EV-mediated dermal inflammation under UVB irradiation. We will test whether melatonin, an
endogenous inhibitor of STING and inflammasomes, suppresses UVB -induced KC-EV production
and dermal inflammation in vivo (3a). We will also assess the mechanism by which melatonin
blocks the ability of KC-EVs to mediate dermal inflammation, i.e., by interfering with STING, the
inflammasome, and/or NF-KB (3b), using experimental systems in vivo and in vitro from Aim 1.
Overall, these aims will reveal a better understanding of the role of epidermis, especially KC-EVs,
in UVB-induced photoaging and skin inflammation, and provide potential novel therapeutic
strategies to prevent and treat these conditions through targeting ...

## Key facts

- **NIH application ID:** 10696367
- **Project number:** 1I01BX005921-01A1
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Rudolph c Johnson
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696367

## Citation

> US National Institutes of Health, RePORTER application 10696367, Extracellular vesicles as a novel mediator for ultraviolet-B light induced photoaging and skin inflammation. (1I01BX005921-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10696367. Licensed CC0.

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