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IL-12 protects from psoriasiform skin inflammation.

Nat. Commun. 7:13466 (2016)
Publishers Version Research data DOI
Open Access Gold
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as soon as is submitted to ZB.
Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed gdT (gdT17) cell subset. We discover that IL-12 receptor signalling in keratinocytes initiates a protective transcriptional programme that limits skin inflammation, suggesting that collateral targeting of IL-12 by anti-p40 monoclonal antibodies is counterproductive in the therapy of psoriasis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Delta T-cells; Interleukin-12/23 Monoclonal-antibody; Chronic Plaque Psoriasis; Necrosis-factor-alpha; Gamma-delta; Interferon-gamma; Epidermal-keratinocytes; Increased Expression; Gene-expression; Cutting Edge
Reviewing status