014 Psoriatic regulatory T cells are impaired in their suppressive activity and respond differently to IL-33

Abstract

Interleukin 33 (IL-33), initially described as an alarmin released by cells following cell damage, can also act immunosuppressive by inducing regulatory T cells (Treg). Disruption of the skin barrier by tape stripping in mice released IL-33 which induced Treg. Accordingly, contact hypersensitivity (CHS) was suppressed upon barrier disruption. Furthermore, blockade of IL-33 enhanced CHS, whereas injection of IL-33 suppressed CHS via induction of Treg. IL-33 is enhanced in the skin and serum of psoriatic patients. On the other hand, in psoriasis Treg are impaired in their suppressive activity. Thus, we asked whether “psoriatic” Treg are impaired in their response to IL-33 in the imiquimod (IMQ)-induced psoriasis like model. IL-33 was enhanced in skin and serum of IMQ-mice. To study the influence of IL-33 on Treg in IMQ-mice, CD4+CD25+ Treg isolated from IMQ or untreated mice were injected into naïve mice which were sensitized 24 h later. Ear challenge was reduced in mice receiving Treg from untreated donors, whereas injection of Treg from IMQ-mice did not cause suppression, implying impairment of Treg in IMQ-mice. To study the response of Treg to IL-33 in IMQ-mice, Treg from untreated or IMQ-mice were incubated with IL-33 and injected into naïve mice which were sensitized thereafter. The suppressive capacity of Treg from WT mice was further enhanced by IL-33, whereas Treg from IMQ mice did not to respond to IL-33. Treg isolated from blood of psoriatic patients were inhibited in their suppressive activity, when compared to Treg from healthy controls. IL-33 induced the expression of Foxp3 in CD4+ T cells obtained from controls, but not in T cells from psoriatic patients. These data confirm that in psoriasis Treg are functionally impaired which may be associated with an altered response to IL-33. The mechanisms responsible for this altered behavior of Treg in psoriasis remain to be elucidated.