Microneedle‐mediated Delivery of Immunomodulators Restores Immune Privilege in Hair Follicles and Reverses Immune‐Mediated Alopecia
Name
Resubmission_Azzi_Artzi_FinalManuscriptAM_final.pdf
Size
6.13 MB
Format
Adobe PDF
Checksum (MD5)
97805d73618b0658c0dcccbb7fd6fea8
Author(s)
Younis, Nour
Puigmal, Núria
Kurdi, Abdallah El
Badaoui, Andrew
Zhang, Dongliang
Morales, Claudia
Saad, Anis
Cruz, Diane
Rahy, Nadim Al
Daccache, Andrea
Date Issued
April 18, 2024
Journal
Advanced Materials
Publisher
Wiley
Citation
N. Younis, N. Puigmal, A. E. Kurdi, A. Badaoui, D. Zhang, C. Morales, A. Saad, D. Cruz, N. A. Rahy, A. Daccache, T. Huerta, C. Deban, A. Halawi, J. Choi, P. Dosta, C. Lian, N. Artzi, J. R. Azzi, Microneedle-mediated Delivery of Immunomodulators Restores Immune Privilege in Hair Follicles and Reverses Immune-Mediated Alopecia. Adv. Mater. 2024, 2312088.
Version
Author's final manuscript
Abstract
Disorders in the regulatory arm of the adaptive immune system result in autoimmune‐mediated diseases. While systemic immunosuppression is the prevailing approach to manage them, it fails to achieve long‐lasting remission due to concomitant suppression of the regulatory arm and carries the risk of heightened susceptibility to infections and malignancies. Alopecia Areata is a condition characterized by localized hair loss due to autoimmunity. The accessibility of the skin provides an opportunity for local rather than systemic intervention to avoid broad immunosuppression. We hypothesized that expansion of endogenous regulatory T cells (Tregs) at the site of antigen encounter can restore the immune balance and generate a long‐lasting tolerogenic response. We therefore utilized a hydrogel microneedle (MN) patch for delivery of CCL22, a chemoattractant for Tregs, and IL‐2, a Treg survival factor to amplify them. In an immune‐mediated murine model of alopecia, we showed local bolstering of Treg numbers leading to sustained hair regrowth and attenuation of inflammatory pathways. In a humanized skin transplant mouse model, we confirmed expansion of Tregs within human skin without engendering peripheral immunosuppression. The MN patch offered high‐loading capacity and shelf‐life stability for prospective clinical translation. By harmonizing immune responses locally, we aspire to reshape the landscape of autoimmune skin disease management.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/adma.202312088
