# Mammalian RNA Exosome in Maintaining Skin Homeostasis and Hair Follicle Immune Privilege

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $396,880

## Abstract

Project Summary
Skin is the first line of defense against many invading microbes, not only acting as a physical barrier, but also
acting as a source of powerful innate immune response. To avoid autoimmune activation in the skin, mammalian
nucleases act as important ‘guardians’ to prevent innate immune sensing of self-nucleic acids. The role of
RNases and RNA degradation machineries in autoimmune skin disease is not well understood. The mammalian
cytoplasmic RNA exosome is a multi-subunits complex consists of RNA helicase SKIV2L and other cofactors.
SKIV2L lost-of-function mutations are associated with Tricho-hepato-enteric Syndrome (THES) in humans, and
THES patients develop remarkable hair and skin abnormalities. In preliminary studies, we generated an inducible
Skiv2l knockout mice (iSkiv2l-/-). iSkiv2l-/- mice develop severe skin inflammation as well as rapid and phenomenal
hair loss (alopecia). The iSkiv2l-/- skin disease is distinct from typical dermatitis or psoriasis, thus representing a
new autoimmune skin disease mouse model. We have two specific aims: Aim 1. Determine the cell type,
endogenous ligand and innate sensing pathway required for activating IFN signaling in iSkiv2l-/- skin. Aim 2.
Determine how innate immune activation of type I IFN breaks immune privilege of hair follicles. Studies proposed
here will provide exciting mechanistic insights in how dysregulated innate immune response to self-RNA could
lead to skin inflammation and hair follicle immune privilege collapse. The iSkiv2l-/- mouse may also have broader
utility in understanding immune privilege and tolerance in the skin that could benefit other autoimmune skin
diseases.

## Key facts

- **NIH application ID:** 10205886
- **Project number:** 1R21AR079147-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Nan Yan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,880
- **Award type:** 1
- **Project period:** 2021-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205886

## Citation

> US National Institutes of Health, RePORTER application 10205886, Mammalian RNA Exosome in Maintaining Skin Homeostasis and Hair Follicle Immune Privilege (1R21AR079147-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10205886. Licensed CC0.

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