Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitis
Psoriasis is a chronic, inflammatory skin disease, frequently associated with dyslipidemia. Lipid disturbance in psoriasis affects both circulatory system and cutaneous tissue. Epidermal Langerhans cells (LCs) are tissue-resident DCs that maintain skin immune surveillance and mediate various cutaneo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-07-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.150223 |
| _version_ | 1818548782617329664 |
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| author | Xilin Zhang Xiaorui Li Yuanyuan Wang Youdong Chen Yijun Hu Chunyuan Guo Zengyang Yu Peng Xu Yangfeng Ding Qing-Sheng Mi Jianhua Wu Jun Gu Yuling Shi |
| author_facet | Xilin Zhang Xiaorui Li Yuanyuan Wang Youdong Chen Yijun Hu Chunyuan Guo Zengyang Yu Peng Xu Yangfeng Ding Qing-Sheng Mi Jianhua Wu Jun Gu Yuling Shi |
| author_sort | Xilin Zhang |
| collection | DOAJ |
| description | Psoriasis is a chronic, inflammatory skin disease, frequently associated with dyslipidemia. Lipid disturbance in psoriasis affects both circulatory system and cutaneous tissue. Epidermal Langerhans cells (LCs) are tissue-resident DCs that maintain skin immune surveillance and mediate various cutaneous disorders, including psoriasis. However, the role of LCs in psoriasis development and their lipid metabolic alternation remains unclear. Here, we demonstrate that epidermal LCs of psoriasis patients enlarge with longer dendrites and possess elevated IL-23p19 mRNA and a higher level of neutral lipids when compared with normal LCs of healthy individuals. Accordantly, epidermal LCs from imiquimod-induced psoriasis-like dermatitis in mice display overmaturation, enhanced phagocytosis, and excessive secretion of IL-23. Remarkably, these altered immune properties in lesional LCs are tightly correlated with elevated neutral lipid levels. Moreover, the increased lipid content of psoriatic LCs might result from impaired autophagy of lipids. Bulk RNA-Seq analysis identifies dysregulated genes involved in lipid metabolism, autophagy, and immunofunctions in murine LCs. Overall, our data suggest that dysregulated lipid metabolism influences LC immunofunction, which contributes to the development of psoriasis, and therapeutic manipulation of this metabolic process might provide an effective measurement for psoriasis. |
| first_indexed | 2024-12-12T08:24:46Z |
| format | Article |
| id | doaj.art-40da961c4c5c4cd8a897ff8a69cd12c0 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T08:24:46Z |
| publishDate | 2022-07-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-40da961c4c5c4cd8a897ff8a69cd12c02022-12-22T00:31:17ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-07-01713Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitisXilin ZhangXiaorui LiYuanyuan WangYoudong ChenYijun HuChunyuan GuoZengyang YuPeng XuYangfeng DingQing-Sheng MiJianhua WuJun GuYuling ShiPsoriasis is a chronic, inflammatory skin disease, frequently associated with dyslipidemia. Lipid disturbance in psoriasis affects both circulatory system and cutaneous tissue. Epidermal Langerhans cells (LCs) are tissue-resident DCs that maintain skin immune surveillance and mediate various cutaneous disorders, including psoriasis. However, the role of LCs in psoriasis development and their lipid metabolic alternation remains unclear. Here, we demonstrate that epidermal LCs of psoriasis patients enlarge with longer dendrites and possess elevated IL-23p19 mRNA and a higher level of neutral lipids when compared with normal LCs of healthy individuals. Accordantly, epidermal LCs from imiquimod-induced psoriasis-like dermatitis in mice display overmaturation, enhanced phagocytosis, and excessive secretion of IL-23. Remarkably, these altered immune properties in lesional LCs are tightly correlated with elevated neutral lipid levels. Moreover, the increased lipid content of psoriatic LCs might result from impaired autophagy of lipids. Bulk RNA-Seq analysis identifies dysregulated genes involved in lipid metabolism, autophagy, and immunofunctions in murine LCs. Overall, our data suggest that dysregulated lipid metabolism influences LC immunofunction, which contributes to the development of psoriasis, and therapeutic manipulation of this metabolic process might provide an effective measurement for psoriasis.https://doi.org/10.1172/jci.insight.150223DermatologyInflammation |
| spellingShingle | Xilin Zhang Xiaorui Li Yuanyuan Wang Youdong Chen Yijun Hu Chunyuan Guo Zengyang Yu Peng Xu Yangfeng Ding Qing-Sheng Mi Jianhua Wu Jun Gu Yuling Shi Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitis JCI Insight Dermatology Inflammation |
| title | Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitis |
| title_full | Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitis |
| title_fullStr | Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitis |
| title_full_unstemmed | Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitis |
| title_short | Abnormal lipid metabolism in epidermal Langerhans cells mediates psoriasis-like dermatitis |
| title_sort | abnormal lipid metabolism in epidermal langerhans cells mediates psoriasis like dermatitis |
| topic | Dermatology Inflammation |
| url | https://doi.org/10.1172/jci.insight.150223 |
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