A Quantitative Increase in Regulatory T Cells Controls Development of Vitiligo
| Autor: | Shikhar Mehrotra, I. Caroline Le Poole, Shilpak Chatterjee, Osama Naga, Hee Kap Kang, Myroslawa Soloshchenko, Jonathan M. Eby, Anuradha K. Murali, Michael I. Nishimura, Amir A. Al-Khami, Navtej Kaur |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Adoptive cell transfer Autoimmunity Vitiligo medicine.disease_cause T-Lymphocytes Regulatory Biochemistry Mice 0302 clinical medicine Depigmentation T-Lymphocyte Subsets Interferon gamma skin and connective tissue diseases Mice Knockout 0303 health sciences education.field_of_study integumentary system Adoptive Transfer 3. Good health 030220 oncology & carcinogenesis Disease Progression Melanocytes Female medicine.symptom Immunosuppressive Agents medicine.drug Genetically modified mouse Receptors CXCR3 Receptors CCR5 Population Mice Transgenic Dermatology Biology Article Proinflammatory cytokine Interferon-gamma 03 medical and health sciences medicine Animals Humans education Molecular Biology 030304 developmental biology Sirolimus Tumor Necrosis Factor-alpha Cell Biology medicine.disease Mice Inbred C57BL Epidermal Cells Immunology Epidermis |
| Zdroj: | The Journal of investigative dermatology |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2013.540 |
| Popis: | T-cell cytolytic activity targeting epidermal melanocytes is shown to cause progressive depigmentation and autoimmune vitiligo. By using the recently developed transgenic mice h3TA2 that carry T cells with a HLA-A2-restricted human tyrosinase peptide (h-Tyr)-reactive TCR and develop spontaneous vitiligo from an early age, we addressed the mechanism regulating autoimmune vitiligo. Depigmentation was significantly impaired only in IFN-γ-knockout h3TA2 mice but not in TNF-α- or perforin-knockout h3TA2 mouse strains, confirming a central role for IFN-γ in vitiligo development. In addition, regulatory T cells (Tregs) were relatively abundant in h3TA2-IFN-γ(-/-) mice, and depletion of the Treg-engaging anti-CD25 antibody fully restored the depigmentation phenotype in h3TA2-IFN-γ(-/-) mice, mediated in part through the upregulation of proinflammatory cytokines such as IL-17 and IL-22. Further therapeutic potential of Treg abundance in preventing progressive depigmentation was evaluated by adoptively transferring purified Treg or using rapamycin. Both the adoptive transfer of Tregs and the use of rapamycin induced a lasting remission of vitiligo in mice treated at the onset of disease, or in mice with established disease. This leads us to conclude that reduced regulatory responses are pivotal to the development of vitiligo in disease-prone mice, and that a quantitative increase in the Treg population may be therapeutic for vitiligo patients with active disease. |
| Databáze: | OpenAIRE |
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