title: α-MSH-stimulated tolerogenic dendritic cells induce functional regulatory T cells and ameliorate ongoing skin inflammation.
abstract: The neuropeptide α-melanocyte-stimulating hormone (α-MSH) is a well-known mediator of skin pigmentation. More recently, it has been shown that α-MSH also exerts a strong anti-inflammatory and immunosuppressive activity. To elucidate the mechanisms underlying α-MSH-induced immunosuppression, we investigated whether α-MSH affects dendritic cell/T cell communication, as especially this interaction has an important role in the regulation of immune responses. Here, we show that α-MSH, by binding to MC-1R, induced tolerogenic dendritic cells, which were capable of expanding CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in vitro, as well as in vivo. Notably, those α-MSH-induced Tregs were functional as they efficiently inhibited cutaneous contact allergy and ongoing psoriasis-like skin inflammation in mice. Furthermore, α-MSH induced tolerogenic dendritic cells capable of generating functional Tregs in human blood. Interestingly, human Tregs expanded via α-MSH-stimulated dendritic cells suppressed the proliferation and cytokine secretion of pathogenic T-helper-17 (Th17) cells from individuals with psoriasis. Taken together, these data indicate that α-MSH induced immunosuppressive Tregs in vitro and in vivo, which inhibited disease progression in a mouse model of psoriasis-like skin inflammation and suppressed the activation and proliferation of effector T cells from subjects with psoriasis.
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Matteo
authors.initials: M
authors.lastname: Auriemma
authors.forename: Thomas
authors.initials: T
authors.lastname: Brzoska
authors.forename: Lars
authors.initials: L
authors.lastname: Klenner
authors.forename: Verena
authors.initials: V
authors.lastname: Kupas
authors.forename: Tobias
authors.initials: T
authors.lastname: Goerge
authors.forename: Maik
authors.initials: M
authors.lastname: Voskort
authors.forename: Zuotao
authors.initials: Z
authors.lastname: Zhao
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Luger
authors.forename: Karin
authors.initials: K
authors.lastname: Loser
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000188:drug therapy*; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000502:physiology; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D044102:Receptor, Melanocortin, Type 1; D000521:alpha-MSH