Summary Interleukin (IL)-23 and CD4+ T helper-17 (Th17) cells are thought to be critical in the development of psoriasis. Here, we report that IL-23 predominantly stimulated dermal γδT cells to produce IL-17 that led to disease progression. Dermal γδT cells constitutively expressed the IL-23 receptor (IL-23R), RORγt, and various chemokine receptors. IL-17 production from dermal γδT cells was independent of αβT cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor δ deficient (Tcrd−/−) and IL-17 receptor deficient (Il17ra−/−) mice but occurred normally in Tcra−/− mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd−/− mice. Perhaps further promoting disease progression, IL-23 stimulated dermal γδT cell expansion. In psoriasis patients, γδT cells were also greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal γδ T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.

Psoriasis is one of the most common immune-mediated chronic, inflammatory skin diseases characterized by hyperproliferative keratinocytes and infiltration of T cells, dendritic cells, macrophages and neutrophils. Although the pathogenesis of psoriasis is not fully understood, there is ample evidence suggesting that the dysregulation of immune cells in the skin, particularly T cells, plays a critical role in psoriasis development. In this review, we mainly focus on the pathogenic T cells and discuss how these T cells are activated and involved in the disease pathogenesis. Newly identified 'professional' IL-17-producing dermal cd T cells and their potential role in psoriasis will also be included. Finally, we will briefly summarize the recent progress on the T cell and its related cytokine-targeted therapy for psoriasis treatment.

On line 8, gd was wrong. It should've read ''.T cells was independent of ab T cells.'' On line 10, d was omitted. It should've read ''.significantly decreased in T cell receptor d-deficient.'' On line 12, Il17ra -/was wrong. It should've read ''.occurred normally in Tcra À/À mice.'' On line 14, Il17ra -/was wrong. It should've read ''.decreased in Tcrd À/À mice.''The authors are sorry for any confusion this may have caused.Additionally, the Note Added in Proof published with this paper online on October 6, 2011 contained the following sentence: ''After acceptance of this manuscript, two studies were published describing a similar population of dermal gd T cells.'' The sentence should've read: ''During review of this manuscript, two studies were published describing a similar population of dermal gd T cells.'' We apologize for any confusion this may have caused.

Dermal IL-17-producing γδT cells play a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal γδT cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. Vγ6T cells are bona fide resident but precursors of dermal Vγ4T cells may require extrathymic environment for imprinting skin homing properties. Thymic Vγ6T cells are more competitive than Vγ4 for dermal γδT cell reconstitution and TCRδ−/− mice reconstituted with Vγ6 develop psoriasis-like inflammation after IMQ-application. Although both IL-23 and IL-1β promote Vγ4 and Vγ6 proliferation, Vγ4 are the main source of IL-17 production, which requires IL-1 signaling. Mice with deficiency of IL-1RI signaling have significantly decreased skin inflammation. These studies reveal a differential developmental requirement and peripheral regulation for dermal Vγ6 and Vγ4 γδT cells, implying a new mechanism that may be involved in skin inflammation.

β-glucans have been reported to function as a potent adjuvant to stimulate innate and adaptive immune responses. However, β-glucans from different sources are differential in their structure, conformation, and thus biologic activity. Different preparations of β-glucans, soluble versus particulate, further complicate their mechanism of action. Here we show that yeast-derived particulate β-glucan activated dendritic cells (DCs) and macrophages via a C-type lectin receptor dectin-1 pathway. Activated DCs by particulate β-glucan promoted Th1 and cytotoxic T-lymphocyte priming and differentiation in vitro. Treatment of orally administered yeast-derived particulate β-glucan elicited potent antitumor immune responses and drastically down-regulated immunosuppressive cells, leading to the delayed tumor progression. Deficiency of the dectin-1 receptor completely abrogated particulate β-glucan-mediated antitumor effects. In contrast, yeast-derived soluble β-glucan bound to DCs and macrophages independent of the dectin-1 receptor and did not activate DCs. Soluble β-glucan alone had no therapeutic effect but significantly augmented antitumor monoclonal antibody-mediated therapeutic efficacy via a complement activation pathway but independent of dectin-1 receptor. These findings reveal the importance of different preparations of β-glucans in the adjuvant therapy and allow for the rational design of immunotherapeutic protocols usable in clinical trials.