MD/PhD Candidate UMass Chan, Mass Gen Brigham Wayland, Massachusetts, United States
Disclosure(s):
Tyler Long: No financial relationships to disclose
Introduction/Rationale: Vitiligo is an autoimmune skin disorder characterized by the progressive destruction of melanocytes, leading to patchy depigmentation. Heligmosomoides polygyrus bakeri is a murine intestinal helminth known for potent immunoregulatory secretions (HES) that promote tolerance across several autoimmune models. Given the central role of Tregs in maintaining peripheral tolerance and their deficiency or dysfunction in vitiligo, we hypothesized that HES could suppress anti-melanocyte immunity by promoting Treg differentiation. In this study, we investigated whether HES treatment could (1) promote functional Treg differentiation in vitro, and (2) inhibit vitiligo pathogenesis in vivo.
Methods: For in vitro studies, naïve mouse CD4+ T cells were cultured for 72h ± HES (10 ug/mL). Foxp3 induction and suppressive capacity were measured by flow cytometry. For in vivo studies, vitiligo was induced in k14*mSCF mice by adoptive transfer of transgenic CD8+ T cells, and animals were treated with purified HES (25 ug 3x per week) or vehicle control. Disease progression was assessed by depigmentation scoring, histology, and flow cytometry of skin, lymph nodes and spleens.
Results: In vitro, HES induced Foxp3 expression from naïve CD4+ T cells but did not cause expansion of existing Treg populations. In vivo, HES-treated mice displayed markedly reduced depigmentation and preserved epidermal melanocytes compared to controls. Flow cytometric analysis revealed increased Foxp3⁺CD25⁺ Tregs and decreased CD8⁺ effector cells in lymphoid tissues.
Conclusion: Together, these findings demonstrate that HES suppresses vitiligo in vivo by promoting regulatory T cell differentiation, suggesting a novel therapeutic approach for autoimmune skin disease.
