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Hiding under the skin: A welcome surprise in psoriasis

Nature Medicine volume 18, pages 1750–1751 (2012)Cite this article

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Until 2005, tissue inflammation associated with T cell activation was considered to originate largely from T helper type 1 (TH1) or TH2 cells, which produce opposing cytokines and may crossregulate each other. However, a major revision to what is known about the mechanisms of T cell inflammation occurred when it was discovered that a new T cell subset, termed TH17 cells (because they produce interleukin-17 (IL-17)), mediates pathogenic inflammation in experimental autoimmune encephalitis, a mouse model of multiple sclerosis1. Until now, it has been an open question whether this population of T cells has a major pathogenic role in any T cell–mediated human disease, such as psoriasis. In mice, TH17 cells selectively synthesize the inflammatory cytokines IL-17 and IL-22. However, in humans, the production of these two cytokines has diverged into two discrete T cell subsets, TH17 and TH22 cells, which produce IL-17 and IL-22, respectively. This finding further expands the potential T cell subsets that could mediate inflammatory disease in humans.

Psoriasis vulgaris is a T cell–mediated inflammatory disease of the skin that affects millions of people across the world2. Affected individuals develop red, raised and scaling skin lesions sometimes affecting the majority of the skin, have a shorter lifespan and are at higher risk of cardiovascular diseases, obesity, metabolic dysregulation/diabetes and psoriatic arthritis3. Psoriasis skin lesions contain excessive numbers of skin-homing T cells that are activated by cutaneous dendritic cells to produce inflammatory cytokines. Activated T cells in psoriasis belong to the TH1, TH17 and TH22 cell subsets defined by the production of interferon-γ (IFN-γ), IL-17A and IL-17F, and IL-22, respectively. In turn, local production of these inflammatory cytokines induces disease-defining epidermal hyperplasia and inflammation by changing the transcriptional profiles of keratinocytes and other types of skin cells (more than 4,000 gene transcripts are altered in psoriasis skin lesions compared to normal adjacent skin)4.

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Figure 1: Skin inflammation in patients with psoriasis and mouse models of disease.

Debbie Maizels

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  1. James G. Krueger is at the Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA.,

    James G Krueger

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  1. James G Krueger
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Correspondence to James G Krueger.

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Competing interests

J.G.K. is a consultant to Eli Lilly, Amgen and Novartis (all are testing IL-17 antagonists in psoriasis).

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Krueger, J. Hiding under the skin: A welcome surprise in psoriasis. Nat Med 18, 1750–1751 (2012). https://doi.org/10.1038/nm.3025

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