IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis

By J. Chan, W. Blumenschein, E. Murphy, Caroline Diveu, M. Wiekowski, S. Abbondanzo, L. Lucian, R. Geissler, S. Brodie, A. Kimball and 6 more. Journal of Experimental Medicine, 2006

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Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor–dependent, but IL-17A–independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23–dependent epidermal hyperplasia was observed in IL-19−/− and IL-24−/− mice, but was inhibited in IL-20R2−/− mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target.

Subfields: Dermatology, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/d3653d39f85333ba1e36212932d33eff9ea486d6

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Citations in the corpus

Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. (2008, background): “IL-17 mRNA has been demonstrated in psoriatic lesions (Teunissen et al., 1998; Li et al., 2004; Chan et al., 2006).”
Review of ustekinumab, an interleukin-12 and interleukin-23 inhibitor used for the treatment of plaque psoriasis (2010, positive): “In a mouse study, direct intradermal injections of IL-23 into normal skin produced erythematous, thick, scaly lesions that demonstrated a mixed dermal infiltrate and epidermal hyperplasia with associated with parakeratosis reminiscent of psoriatic plaques on histological analysis; although, injectio”
Circulating Th17, Th22, and Th1 Cells Are Increased in Psoriasis (2009, positive): “These cells and the cytokines produced by these cells are found in increased levels within skin affected by psoriasis (Chan et al., 2006; Wolk et al., 2006; Wilson et al., 2007; Zaba et al., 2007; Kryczek et al., 2008; Lowes et al., 2008; Harper et al., 2009).”
Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. (2012, neutral): “Nasopharyngitis 5 (19) 3 (11) 3 (10) 3 (10) 4 (14)”
Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. (2007, background): “Recent work in our laboratory has extended this early work and shown that when delivered intradermally in mice, IL-23 essentially triggers what amounts to a woundhealing response (32).”
The IL-23/Th17 axis in the immunopathogenesis of psoriasis. (2009, background): “Intradermal injection of IL-23 in mice led to erythema, induration, and prominent dermal papillary blood vessels with histopathological features resembling psoriasis (Chan et al., 2006).”
Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis1 (2009, background): “Intradermal injection of IL-23 in mouse skin induces several features of psoriatic skin such as erythema, an inflammatory infiltrate, and acanthosis (23, 24).”