Granzyme A potentiates chemokine production in IL‐17‐stimulated keratinocytes |
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| Authors: | Stanley Cheuk Elisa Martini Kerstin Bergh David Chang Bence Rethi Mona Ståhle Liv Eidsmo |
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| Affiliation: | 1. Dermatology and Venereology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden;2. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden |
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| Abstract: | Plaque psoriasis presents with focal skin inflammation, partially maintained by IL‐17‐mediated interactions between infiltrating epidermal T cells and activated keratinocytes. Here we show that the majority of lesional epidermal CD8 T cells express granzyme A, alone or in combination with IL‐17. To assess proinflammatory properties of granzyme A in psoriasis, primary human keratinocytes were stimulated with granzyme A in the presence or absence of IL‐17. Out of 33 analysed keratinocyte‐derived inflammatory mediators, granzyme A potentiated IL‐17‐induced secretion of CXCL 1, CXCL 12 and CCL 4. Intriguingly, all three chemokines are implicated in psoriasis pathogenesis and are involved in recruitment of T cells, neutrophils and pDCs into inflamed tissues. Our results indicate that granzyme A produced by lesional CD8 T cells specifically increase the chemokine production from inflamed keratinocytes, thereby amplifying a chemotactic inflammatory loop that sustains psoriasis lesions. |
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| Keywords: | cytotoxic granules inflammation psoriasis serine proteases T cells |
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