Replenishing Regulatory T Cells to Halt Depigmentation in VitiligoVitiligo is a cutaneous autoimmune disease, especially devastating to patients with darker skin tones because of the contrast between unaffected and lesional skin. We studied immune cells infiltrating vitiligo skin and found very few regulatory T cells (Tregs). Vitiligo was not associated with a reduced frequency or function of circulating Tregs. To manipulate Treg function, we used mouse models expressing melanocyte-reactive TCRs, following changes in pelage color. We also isolated splenocytes to measure Treg function and evaluated cutaneous Treg abundance.
Combining Type I Interferons and 5-Aza-2′-Deoxycitidine to Improve Anti-Tumor Response against MelanomaResistance to IFN-I–induced antineoplastic effects has been reported in many tumors and arises, in part, from epigenetic silencing of IFN-stimulated genes by DNA methylation. We hypothesized that restoration of IFN-stimulated genes by co-administration of the demethylating drug 5-aza-2′-deoxycitidine (decitabine [DAC]) may enhance the susceptibility to IFN-I–mediated antitumoral effects in melanoma. We show that combined administration of IFN-I and DAC significantly inhibits the growth of murine and human melanoma cells, both in vitro and in vivo.
Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor MechanismsPsoriasis vulgaris is an inflammatory skin disease caused by hyperactivated T cells regulated by positive and negative mechanisms; although the former have been much studied, the latter have not. We studied the regulatory mechanism mediated by myeloid-derived suppressor cells (MDSCs) and showed that MDSCs expanded in melanoma patients express dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand, a critical mediator of T-cell suppressor function. We examined expansion of DC-HIL+ MDSCs in psoriasis and characterized their functional properties.
Increased, but Functionally Impaired, CD14+ HLA-DR–/low Myeloid-Derived Suppressor Cells in Psoriasis: A Mechanism of Dysregulated T CellsThe clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14+ HLA-DR–/low monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis.