Macrophages mediate psoriasis via Mincle-dependent mechanism in mice
Abstract Psoriasis is currently considered to be an immune and inflammatory disease characterized by massive immune cells infiltration including macrophages. It has been reported that macrophage-inducible C-type lectin (Mincle) is essential to maintain the pro-inflammatory phenotype of M1 macrophage...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01444-8 |
| _version_ | 1797836649164439552 |
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| author | Rui-zhi Tan Xia Zhong Rang-yue Han Ke-huan Xie Jian Jia Ye Yang Mei Cheng Chun-yan Yang Hui-yao Lan Li Wang |
| author_facet | Rui-zhi Tan Xia Zhong Rang-yue Han Ke-huan Xie Jian Jia Ye Yang Mei Cheng Chun-yan Yang Hui-yao Lan Li Wang |
| author_sort | Rui-zhi Tan |
| collection | DOAJ |
| description | Abstract Psoriasis is currently considered to be an immune and inflammatory disease characterized by massive immune cells infiltration including macrophages. It has been reported that macrophage-inducible C-type lectin (Mincle) is essential to maintain the pro-inflammatory phenotype of M1 macrophages, however, its role and mechanisms in psoriasis remain largely unknown. A model of psoriasis was induced in mice by a daily topical application of imiquimod for 7 days. Role and mechanisms of Mincle in macrophage-mediated psoriasis were investigated in clodronate liposomes induced macrophage depletion mice followed by adoptively transferring with Mincle-expressing or -knockout (KO) macrophages, and in macrophage specific Mincle knockout mice (Mincleloxp/loxp/Lyz2-cre+/+). Finally, a Mincle neutralizing antibody was employed to the psoriasis mice to reveal the therapeutic potential for psoriasis by targeting Mincle. Mincle was highly expressed by M1 macrophages in the skin lesions of patients and mice with psoriasis. Clodronate liposomes-induced macrophage depletion inhibited psoriasis in mice, which was restored by adoptive transfer with Mincle-expressing macrophages but not by Mincle-KO macrophages. This was further confirmed in macrophage-specific Mincle-KO mice. Mechanistically, macrophages mediated psoriasis via the Mincle-Syk-NF-κB pathway as blocking macrophage Mincle inhibited Syk/NF-κB-driven skin lesions and epidermal injury in vivo and in vitro. We also found that LPS induced Mincle expression by M1 macrophages via the PU.1-dependent mechanism. Most importantly, we revealed that targeting Mincle with a neutralizing antibody significantly improved psoriasis in mice. In summary, our findings demonstrated that macrophages mediate psoriasis in mice via the Mincle-dependent mechanism, targeting Mincle may represent as a novel therapy for psoriasis. A simplified pathway model of Mincle in macrophage-mediated psoriasis. |
| first_indexed | 2024-04-09T15:13:24Z |
| format | Article |
| id | doaj.art-e528d26615094b3fbfa22f46e1fc16f4 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-09T15:13:24Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-e528d26615094b3fbfa22f46e1fc16f42023-04-30T11:07:31ZengNature Publishing GroupCell Death Discovery2058-77162023-04-019111310.1038/s41420-023-01444-8Macrophages mediate psoriasis via Mincle-dependent mechanism in miceRui-zhi Tan0Xia Zhong1Rang-yue Han2Ke-huan Xie3Jian Jia4Ye Yang5Mei Cheng6Chun-yan Yang7Hui-yao Lan8Li Wang9Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityResearch Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityResearch Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityResearch Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityResearch Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Orthopaedics, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDermatological Department, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDermatological Department, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong KongResearch Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAbstract Psoriasis is currently considered to be an immune and inflammatory disease characterized by massive immune cells infiltration including macrophages. It has been reported that macrophage-inducible C-type lectin (Mincle) is essential to maintain the pro-inflammatory phenotype of M1 macrophages, however, its role and mechanisms in psoriasis remain largely unknown. A model of psoriasis was induced in mice by a daily topical application of imiquimod for 7 days. Role and mechanisms of Mincle in macrophage-mediated psoriasis were investigated in clodronate liposomes induced macrophage depletion mice followed by adoptively transferring with Mincle-expressing or -knockout (KO) macrophages, and in macrophage specific Mincle knockout mice (Mincleloxp/loxp/Lyz2-cre+/+). Finally, a Mincle neutralizing antibody was employed to the psoriasis mice to reveal the therapeutic potential for psoriasis by targeting Mincle. Mincle was highly expressed by M1 macrophages in the skin lesions of patients and mice with psoriasis. Clodronate liposomes-induced macrophage depletion inhibited psoriasis in mice, which was restored by adoptive transfer with Mincle-expressing macrophages but not by Mincle-KO macrophages. This was further confirmed in macrophage-specific Mincle-KO mice. Mechanistically, macrophages mediated psoriasis via the Mincle-Syk-NF-κB pathway as blocking macrophage Mincle inhibited Syk/NF-κB-driven skin lesions and epidermal injury in vivo and in vitro. We also found that LPS induced Mincle expression by M1 macrophages via the PU.1-dependent mechanism. Most importantly, we revealed that targeting Mincle with a neutralizing antibody significantly improved psoriasis in mice. In summary, our findings demonstrated that macrophages mediate psoriasis in mice via the Mincle-dependent mechanism, targeting Mincle may represent as a novel therapy for psoriasis. A simplified pathway model of Mincle in macrophage-mediated psoriasis.https://doi.org/10.1038/s41420-023-01444-8 |
| spellingShingle | Rui-zhi Tan Xia Zhong Rang-yue Han Ke-huan Xie Jian Jia Ye Yang Mei Cheng Chun-yan Yang Hui-yao Lan Li Wang Macrophages mediate psoriasis via Mincle-dependent mechanism in mice Cell Death Discovery |
| title | Macrophages mediate psoriasis via Mincle-dependent mechanism in mice |
| title_full | Macrophages mediate psoriasis via Mincle-dependent mechanism in mice |
| title_fullStr | Macrophages mediate psoriasis via Mincle-dependent mechanism in mice |
| title_full_unstemmed | Macrophages mediate psoriasis via Mincle-dependent mechanism in mice |
| title_short | Macrophages mediate psoriasis via Mincle-dependent mechanism in mice |
| title_sort | macrophages mediate psoriasis via mincle dependent mechanism in mice |
| url | https://doi.org/10.1038/s41420-023-01444-8 |
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