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Peer-reviewedCC BY 4.0Pigment Cell & Melanoma Research

Females Display Greater Disease Severity in a Mouse Model of Vitiligo

  • Kaitlyn G. O'Donnell1
  • Zhussipbek Mukhatayev2
  • Hanin Abuzer2
  • Rohan S. Shivde2
  • Sriram Saravanan Shanmugavelandy2
  • Octavio K. Bartos2
  • Ellis Kang2
  • Emilia R. Dellacecca3
  • Dinesh Jaishankar4
  • Surya Pandey5
  • Hee Kap Kang6
  • Ziyou Ren2
1 more authors
  • I. Caroline Le Poole2
6 affiliations
  1. 1Indiana University School of Medicine Indianapolis Indiana USA
  2. 2Department of Dermatology, Microbiology and Immunology, Feinberg School of Medicine Northwestern University Chicago Illinois USA
  3. 3Mayo Clinic College of Medicine and Science, Mayo Clinic Rochester Minnesota USA
  4. 4Department of Surgery, Feinberg School of Medicine Northwestern University Chicago Illinois USA
  5. 5Department of Hematology and Oncology, Feinberg School of Medicine Northwestern University Chicago Illinois USA
  6. 6Department of Pediatrics, Lurie Children's Hospital Northwestern University Chicago Illinois USA
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Abstract

Vitiligo is an autoimmune disease characterized by progressive depigmentation of the skin due to T cell‐mediated destruction of melanocytes. Disease onset varies but usually initiates during adolescence. Sex differences in disease development and therapeutic outcomes have not been explored. We previously associated stress induced HSP70i with immune activation in depigmentation and showed that HSP70iQ435A can tolerize dendritic cells (DCs) to prevent cutaneous recruitment and activation of T cells. Among male and female vitiligo‐prone mice, we investigated the long‐term efficacy of HSP70iQ435A plasmid DNA treatment introduced by biolistic administration at varying stages of vitiligo development. Mice were followed up to 46 weeks of age. Female mice exhibited 1.89‐fold greater depigmentation than males overall, while both responded proportionally to treatment with effects lasting throughout. This sex difference was associated with significantly elevated IFN‐γ secretion by melanocyte‐reactive T cells among female mice. Humoral responses to the protein remained readily detectable at end point regardless of treatment interval. These findings also suggest greater benefit from earlier intervention.

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Cite

BibTeXRIS
BibTeX
@article{odonnell2026females,
  title = {{Females Display Greater Disease Severity in a Mouse Model of Vitiligo}},
  author = {Kaitlyn G. O'Donnell and Zhussipbek Mukhatayev and Hanin Abuzer and Rohan S. Shivde and Sriram Saravanan Shanmugavelandy and Octavio K. Bartos and Ellis Kang and Emilia R. Dellacecca and Dinesh Jaishankar and Surya Pandey and Hee Kap Kang and Ziyou Ren and I. Caroline Le Poole},
  journal = {Pigment Cell \& Melanoma Research},
  year = {2026},
  month = nov,
  doi = {10.1111/pcmr.70134},
  url = {https://doi.org/10.1111/pcmr.70134},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Females Display Greater Disease Severity in a Mouse Model of Vitiligo
AU  - Kaitlyn G. O'Donnell
AU  - Zhussipbek Mukhatayev
AU  - Hanin Abuzer
AU  - Rohan S. Shivde
AU  - Sriram Saravanan Shanmugavelandy
AU  - Octavio K. Bartos
AU  - Ellis Kang
AU  - Emilia R. Dellacecca
AU  - Dinesh Jaishankar
AU  - Surya Pandey
AU  - Hee Kap Kang
AU  - Ziyou Ren
AU  - I. Caroline Le Poole
PY  - 2026
DA  - 2026/11/05
JO  - Pigment Cell & Melanoma Research
DO  - 10.1111/pcmr.70134
UR  - https://doi.org/10.1111/pcmr.70134
AB  - Vitiligo is an autoimmune disease characterized by progressive depigmentation of the skin due to T cell‐mediated destruction of melanocytes. Disease onset varies but usually initiates during adolescence. Sex differences in disease development and therapeutic outcomes have not been explored. We previously associated stress induced HSP70i with immune activation in depigmentation and showed that HSP70iQ435A can tolerize dendritic cells (DCs) to prevent cutaneous recruitment and activation of T cells. Among male and female vitiligo‐prone mice, we investigated the long‐term efficacy of HSP70iQ435A plasmid DNA treatment introduced by biolistic administration at varying stages of vitiligo development. Mice were followed up to 46 weeks of age. Female mice exhibited 1.89‐fold greater depigmentation than males overall, while both responded proportionally to treatment with effects lasting throughout. This sex difference was associated with significantly elevated IFN‐γ secretion by melanocyte‐reactive T cells among female mice. Humoral responses to the protein remained readily detectable at end point regardless of treatment interval. These findings also suggest greater benefit from earlier intervention.
SN  - 1755-1471
SN  - 1755-148X
ER  -