# IL-27 and downstream mechanisms in Alopecia Areata

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $336,501

## Abstract

PROJECT SUMMARY
 Alopecia areata (AA) is a common autoimmune disease in which the hair follicle is the target of attack
and results clinically in hair loss. Despite the associated high lifetime risk of approximately 2% and its substantive
psychosocial impact, no FDA approved treatments exist for AA. The lack of effective options for the population
that suffers from this disfiguring disease with significant psychosocial ramifications represents a significant unmet
medical need.
 The absence of approved treatments is in part due to an incomplete understanding of the unbalanced
equilibrium between pathogenic immune responses and immunoregulatory mechanisms that prevent
autoimmunity in AA. Although many cytokines, pathways, and cell types have been hypothesized to prevent
immune attack of the hair follicle, it is unknown what factors participate in regulating autoimmune responses in
vivo. Identifying these critical immunoregulatory participants may not only deepen our understanding of AA
pathogenesis, but may reveal anti-inflammatory pathways that may be exploited to develop novel approaches to
treatment.
 IL-27 is a cytokine with immunoregulatory properties that has been studied in various autoimmune,
infectious, and tumor models. The receptor for IL-27 is expressed by a wide array of immune cell types as well
as epithelial and endothelial cells, supporting its potential to modulate the immune system and critical cell
types that interact with the immune system. In particular, IL-27 has been shown to dampen conventional T cell
responses, increase the number of regulatory T cells, and induce naïve and previously activated CD4 and CD8
T cells to produce IL-10, a well-known cytokine with anti-inflammatory effects in most contexts. Our
preliminary data indicate that overexpression of IL-27 can substantially prevent the development of murine AA,
and further analysis revealed regulatory T cells and IL-10 as potential downstream candidates participating in
disease suppression.
 We propose to study the mechanisms of AA suppression of exogenous IL-27 and its downstream
effects on regulating immune responses to the hair follicle and preventing the development of AA. We have
adopted and further developed a spontaneous AA mouse model to robustly develop disease in an inducible,
controlled, and well-characterized manner by adoptive transfer of activated pathogenic T cells. Combining our
AA model with newly developed genetic tools will allow us to dissect the mechanisms by which IL-27 may be
used to ablate AA pathogenesis and has the potential to reveal novel therapeutic strategies.

## Key facts

- **NIH application ID:** 10490304
- **Project number:** 5R01AR077194-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Ali Jabbari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $336,501
- **Award type:** 5
- **Project period:** 2021-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490304

## Citation

> US National Institutes of Health, RePORTER application 10490304, IL-27 and downstream mechanisms in Alopecia Areata (5R01AR077194-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10490304. Licensed CC0.

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