Rorγt+ innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in mice
Stanislav Pantelyushin, … , Alexander A. Navarini, Burkhard Becher
Stanislav Pantelyushin, … , Alexander A. Navarini, Burkhard Becher
Published June 1, 2012; First published May 1, 2012
Citation Information: J Clin Invest. 2012;122(6):2252-2256. https://doi.org/10.1172/JCI61862.
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Categories: Brief Report Dermatology

Rorγt+ innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in mice

Abstract

Psoriasis is a common, relapsing inflammatory skin disease characterized by erythematous scaly plaques. Histological manifestations of psoriasis include keratinocyte dysregulation and hyperproliferation, elongated rete ridges, and inflammatory infiltrates consisting of T cells, macrophages, dendritic cells, and neutrophils. Despite the availability of new effective drugs to treat psoriasis, the underlying mechanisms of pathogenesis are still poorly understood. Recent studies have shown that Aldara cream, used to treat benign skin abnormalities, triggers psoriasis-like disease in humans and mice and have implicated Th17 cells in disease initiation. Using this as a model, we found a predominant role for the Th17 signature cytokines IL-17A, IL-17F, and IL-22 in psoriasiform plaque formation in mice. Using gene-targeted mice, we observed that loss of Il17a, Il17f, or Il22 strongly reduced disease the severity of psoriasis. However, we found that Th17 cells were not the primary source of these pathogenic cytokines. Rather, IL-17A, IL-17F, and IL-22 were produced by a skin-invading population of γδ T cells and RORγt+ innate lymphocytes. Furthermore, our findings establish that RORγt+ innate lymphocytes and γδ T cells are necessary and sufficient for psoriatic plaque formation in an experimental disease model that closely resembles human psoriatic plaque formation.

Authors

Stanislav Pantelyushin, Stefan Haak, Barbara Ingold, Paulina Kulig, Frank L. Heppner, Alexander A. Navarini, Burkhard Becher

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Figure 1

IL-17A, IL-17F, and IL-22 are important for psoriatic plaque formation.

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IL-17A, IL-17F, and IL-22 are important for psoriatic plaque formation. ...
(A and B) WT mice were treated with Aldara and anti–IL-12/23p40 mAb or isotype control on day 2. (A) Kinetics of skin inflammation as percent increase in thickness over 6 days (n = 4). (B) Skin sections were stained with H&E and anti-MPO. Scale bars: 100 μm. (C) Dot plots display the secretion of IL-17A, IL-17F, and IL-22 among CD45+ cells from the skin of wild-type mice on day 5 of Aldara treatment. (D and E) WT, Il17a–/–, Il17f–/–, and Il22–/– mice were treated with Aldara or control cream for 5 days. Scatter plot shows percent increase in skin thickness (n = 4) (D). Skin sections of Aldara-treated mice taken on day 6 (E) were stained with H&E. Scale bar: 100 μm. (F) IL-17AF heterodimer concentration was measured in the supernatant of LN or skin cells cultured for 24 hours using IL-17AF FlowCytomix Simplex kit (eBioscience). Each experiment was performed independently at least 3 times. *P < 0.05, **P < 0.01, #P < 0.001.