Oral communication, CS11 / C49
Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011
A hot finding: mutant HSP70i to treat vitiligo
| SPEAKER | J. Mosenson #whois submiter ? |
| AUTHOR(s) | J. Mosenson, A. Zloza, J. Klarquist, S. Mehrotra, M. Nishimura, J.A. Guevara-Patino, I.C. Le Poole |
Vitiligo is a T cell mediated autoimmune disease of the skin that results in progressive depigmentation. We have previously shown that inducible heat shock protein 70 (HSP70i) is required to drive autoimmune depigmentation, with crucial involvement of amino acid residues 435-445. Here we evaluated depigmentation in vitiligo-prone mice vaccinated with HSP70i with and without a base pair mutation in this dendritic cell (DC) activating region. Wild-type C57BL/6 mice and vitiligo-prone strains transgenic for melanocyte-reactive T cell receptors: Pmel-1 (depigmentation initiating >6 months of age) and h3TA2 (progressive vitiligo by 4 weeks of age) were gene gun vaccinated with HSP70iQ435A, wild-type HSP70i, or empty vector DNA, and evaluated for depigmentation of the pelage. DCs were phenotyped by FACS analysis. Vitiligo-prone Pmel-1 mice displayed significantly increased depigmentation in response to wild-type HSP70i alone. Importantly, mutant HSP70iQ435A fully abrogated the depigmentation response, supporting the prophylactic potential of mutant HSP70i. In actively depigmenting h3TA2 mice, further depigmentation was visible within 4 weeks after HSP70i vaccination. In animals vaccinated with HSP70iQ435A however, a fully pigmented pelage returned. FACS analysis of non-lymphocyte splenocytes harvested from Pmel-1 mice 6 months after vaccination revealed distinct monocyte derivative cell populations with differing levels of CD11c and CD11b expression. The abundance of cells with an immunosuppressive phenotype significantly increased after vaccination with mutant HSP70i, whereas an opposite trend was observed for the inflammatory DC population. Together, these data support sustained effects of HSP70iQ435A on dendritic cells in vitiligo-prone mice and highlight the treatment potential of HSP70i with a single base pair mutation for progressive vitiligo.
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