期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 141, 期 7, 页码 1707-+出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2021.01.005
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资金
- Janssen Research & Development and Innovaderm
This study identified the major IL-23+ mononuclear phagocyte and IL-17+T-cell subsets in psoriatic skin lesions, as well as revealed the changes in cellular composition before and during treatment with guselkumab or secukinumab.
Cellular sources of IL-23 and IL-17A driving skin inflammation in psoriasis remain unclear. Using highdimensional unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions of patients before and during guselkumab (IL-23p19 blocker) or secukinumab (IL-17A blocker) treatment. Among CD11c+HLA-DR+ mononuclear phagocytes, CD64brightCD163-CD14brightCD1c-CD1a- inflammatory monocyte-like cells were the predominant IL-23-producing cells and, together with CD64-CD163-CD14-IL-23p19-TNF-a+ inflammatory dendritic cell-like cells, were increased in lesional compared with those in nonlesional skin taken from the same patient. Within T cells, CD8+CD49a+ and/or CD103+ tissue-resident memory T cells, CD4+CD25+FoxP3+ regulatory T cells, and CD4+CD49a-CD103- T cells were increased. Moreover, CD4+CD49a-CD103- T cells and the relatively rare CD8+ memory T cells equally contributed to IL-17A production. Both treatments decreased the frequencies of inflammatory monocyte-like, inflammatory dendritic cell-like, and CD4+CD49a-CD103- T cells. In contrast, guselkumab reduced memory T cells while maintaining regulatory T cells and vice versa for secukinumab. Neither drug modified the frequencies of IL-17A+IL-17F+/- CD4+ or CD8+ T cells. This study reveals the identity of the major IL-23+ mononuclear phagocyte and IL-17+T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL-23/IL-17A pathway in psoriasis.
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