Abstract
0054 Treg-targeted therapies restrain disease in a murine model of alopecia areata
Journal of investigative dermatology, Vol.145(8 Suppl), pp.S9-S9
08/2025
DOI: 10.1016/j.jid.2025.06.055
Abstract
Alopecia Areata (AA) is a common autoimmune disease that presents as nonscarring hair loss. Current FDA-approved treatments for AA are limited to JAK inhibitors; however, potential adverse effects and refractory patients invites the development of alternative therapeutic strategies. Our lab has shown that selective depletion of regulatory T cells (Tregs) in the C3H/HeJ murine model of AA enhances disease development, suggesting that Tregs may play a role in defending the hair follicle from attack. We have also observed that emergence of disease is marked by a robust expansion of CD8 effector T cells (Teffs) that results in this population outnumbering Tregs 20-fold. We hypothesized that pharmacologic enhancement of the Treg pool may be an effective strategy for modulating disease. While low dose recombinant human IL-2 (hIL-2) for the purpose of Treg expansion has not shown great promise for AA patients, IL-2 fusion proteins have shown benefits in other disease models and offer advantages over hIL-2. HCW9302 is a recombinant fusion protein containing two human IL-2 domains fused to a soluble human tissue factor domain. It has a longer half-life than hIL-2 and can selectively expand and activate either human or murine Tregs. Using a murine skin-graft induction model of AA, we observed HCW9302 treatment protected mice from developing AA. We also noted a significant reduction in the number of Teff found infiltrating the skin and a recovery of skin Tregs to outnumber Teff 4:1. Overall, our findings suggest that Tregs play a protective role towards the hair follicle, and their enhancement is effective at restraining disease. Our data provides translational support for the use of IL-2 fusion proteins as a therapeutic strategy for patients with AA.
Details
- Title: Subtitle
- 0054 Treg-targeted therapies restrain disease in a murine model of alopecia areata
- Creators
- M. Lensing - University of IowaS.J. Connell - University of IowaP. Rhode - HCW Biologics, Miramar, Florida, United StatesN. Shrestha - HCW Biologics, Miramar, Florida, United StatesX. Zhu - HCW Biologics, Miramar, Florida, United StatesH.C. Wong - HCW Biologics, Miramar, Florida, United StatesA. Jabbari - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Journal of investigative dermatology, Vol.145(8 Suppl), pp.S9-S9
- DOI
- 10.1016/j.jid.2025.06.055
- ISSN
- 0022-202X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 08/2025
- Academic Unit
- Dermatology; Neuroscience and Pharmacology
- Record Identifier
- 9984848118102771
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