Stat3 activation in epidermal keratinocytes induces psoriasis-like lesions via activation and migration of Langerhans cells to skin draining lymph nodes.
| Project/Area Number |
15K09769
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kochi University |
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Principal Investigator |
Nakajima Kimiko 高知大学, 教育研究部医療学系臨床医学部門, 准教授 (20403892)
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| Co-Investigator(Kenkyū-buntansha) |
山本 真有子 高知大学, 教育研究部医療学系臨床医学部門, 助教 (20423478)
中島 英貴 高知大学, 教育研究部医療学系臨床医学部門, 講師 (70314995)
佐野 栄紀 高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 乾癬 / 皮膚バリア障害 / Stat3 / Langerhans細胞 / バリア障害 |
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| Outline of Final Research Achievements |
Langerhans cells (LCs) were activated in psoriatic lesion of patients with psoriasis and psoriasis-like lesions of K5.Stat3C mice treated with 12-O-tetradecanoylphorbol
-13-acetate (TPA). Notably, compared with nontransgenic mice, K5.Stat3C mice showed an increased number of LCs in the sDLNs before psoriasis-like lesions developed. Importantly, the psoriasis-like lesions in K5.Stat3C mice_langerin DTR KI mice were significantly attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesions. Flow cytometric analysis of cells from sDLNs in TPA treated-K5.Stat3C mice revealed that LCs produced IL-23. Moreover, IL-1α was up-regulated in keratinocytes of Stat3C mice. Our study suggests that Stat3 activation in keratinocytes induces the activation of LCs and that migration of LCs to sDLNs is essential for the pathogenesis of psoriasis through producing inflammatory cytokines such as IL-23.
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Report
(4 results)
Research Products
(15 results)
