Nakajima K.Critical role of the interleukin-23/T-helper 17 cell axis in the pathogenesis of psoriasis. J Dermatol 39:219-224

Department of Dermatology, Kochi Medical School, Kochi University, Kochi, Japan.
The Journal of Dermatology (Impact Factor: 2.25). 03/2012; 39(3):219-24. DOI: 10.1111/j.1346-8138.2011.01458.x
Source: PubMed


Psoriasis is an inflammatory disease with dynamic interactions between the immune system and the skin. Recent studies have demonstrated that the interleukin (IL)-23/T-helper (Th)17 cell axis plays an important role in the pathogenesis of psoriasis. Here, the biology and function of Th17 cells as well as the crucial role of IL-23 in the context of the Th17 cell-dependent chronic inflammation in psoriatic skins are reviewed. Recent study about the role of the IL-23/Th17 axis in the pathogenesis of psoriasis-like lesions in K5.Stat3C transgenic mice is also discussed. This model mouse for psoriasis not only verifies the therapeutic efficacies of biologics that specifically target the IL-23/Th17 axis, but also clarifies the pathogenesis of psoriasis.

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    • "In psoriasis, IL-23 is produced at high levels by DCs and keratinocytes, and this cytokine stimulates Th17 cells to produce IL-17A and IL-22. Several groups reported that psoriatic lesions showed increased mRNA levels of the IL- 23/Th17 axis, including IL-23p19, IL-12/23p40, IL-22, IL-17A, and IL-17F, whereas mRNA levels of IL-12p35 and IL-4 were not elevated [24] [25] [26]. Furthermore, evidence for the role of IL-23 in the pathogenesis of psoriasis was substantiated by the initiation of the psoriasis-like disease acanthosis following repeated injections of IL-23 in mice [12]. "
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    ABSTRACT: T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF- α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.
    Clinical and Developmental Immunology 07/2013; 2013(14):968549. DOI:10.1155/2013/968549 · 2.93 Impact Factor
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    ABSTRACT: Sjögren's syndrome (SjS) is a systemic autoimmune disease that primarily targets salivary and lacrimal glands. SjS affects 2-4 million people in the US alone and greatly affects the life quality of the afflicted individuals. Autoreactive effector T cells are central executors and orchestrators in the pathogenic processes of SjS by mediating target organ inflammation and destruction and by facilitating B cell responses and autoantibody production. A variety of cytokines that are produced by effector T cells or capable of directly affecting effector T cells are elevated in the target organs and circulations of SjS patients. The recent advancement in the understanding about the functions of these cytokines, achieved by using both human samples and mouse disease models, has generated great insights into the cytokine control of autoimmune responses in the SjS disease setting. In this review, we summarized the recent findings on the expression and functions of cytokines in this disease, with specific focus on those derived from T cells and/or directly affecting T cell responses.
    02/2013; S!(9). DOI:10.4172/2155-9899.S1-009
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    ABSTRACT: It has been recognized that ceramides are decreased in the epidermis of patients with psoriasis as well as atopic dermatitis. Here, we generated Sptlc2 (serine palmitoyltransferase long chain base subunit 2) targeted mice (SPT-cKO mice), thereby knocking out serine palmitoyltransferase (SPT), the critical enzyme for ceramide biosynthesis, in keratinocytes. SPT-cKO mice showed decreased ceramide levels in the epidermis, which impaired water-holding capacity and barrier function. From 2 weeks of age, they developed skin lesions with histologic aberrations including hyperkeratosis, acanthosis, loss of the granular layer, inflammatory cell infiltrates. Epidermal Langerhans cells showed persistent activation and enhanced migration to lymph nodes. Skin lesions showed up-regulation of psoriasis-associated genes, such as IL-17A, IL-17F, IL-22, S100A8, S100A9 and β-defensins. In the skin lesions and draining lymph nodes, there were increased numbers of γδ T cells that produced IL-17 (γδ-17 cells), most of which also produced IL-22, as do Th17 cells. Furthermore, IL-23-producing CD11c(+) cells were observed in the lesions. In vivo treatment of SPT-cKO mice with an anti-IL-12/23p40 antibody ameliorated the skin lesions and reduced the numbers of γδ-17 cells. Therefore, we conclude that a ceramide deficiency in the epidermis leads to psoriasis-like lesions in mice, likely mediated by IL-23-dependent IL-22-producing γδ-17 cells.Journal of Investigative Dermatology accepted article preview online, 30 April 2013; doi:10.1038/jid.2013.199.
    Journal of Investigative Dermatology 04/2013; 133(11). DOI:10.1038/jid.2013.199 · 7.22 Impact Factor
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