| Project/Area Number |
22K15126
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44020:Developmental biology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Discontinued (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Il1r2 / Dlx1 / TPA / skin inflammation / IL-1R2 / Tet-on system / Epidermal Stem Cells / Chronic inflammation |
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| Outline of Research at the Start |
In this project, the behavior of the newly identified IL-1R2+ stem cell population during aging will be investigated using a newly generated knock-in Il1r2-CreER line. Aging phenotypes in the Il1r2 conditional knockout and over-expression mice will be investigated. Finally, the molecular mechanism of the inflammatory response of epidermal stem cells via IL-1 signaling will be examined by testing downstream factors in primary keratinocytes.
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| Outline of Annual Research Achievements |
We have successfully generated mouse models with Il1r2 overexpression (pTRE-Il1r2/Rosa-rtTA). In these mice, Il1r2 overexpression mitigated TPA-induced skin inflammation, leading to reduced epidermal thickness, cell proliferation, and inflammatory cytokines (Il1a) when compared to wild-type control mice. Conversely, Il1r2-KO (Il1r2CreERT2) mice did not exhibit phenotypes under basal conditions or TPA-induced skin inflammation compared to their wild-type counterparts.
To observe the behavior of Il1r2-expressing basal cells in tail skin during TPA-induced skin inflammation, we utilized Il1r2CreERT2/Rosa-Td(ts) mouse models. Whole-mount staining of the tail skin revealed that, during TPA-induced inflammation, the size of Il1r2-expressing clones (Il1r2 clones) increased in comparison to Ethanol-treated tail skin. Immunofluorescence staining of tail skin sections demonstrated that under TPA-induced inflammation, Il1r2 clones at the basal layer underwent proliferation and migration toward the upper layers of the tail skin. Notably, under TPA-induced skin inflammation, the behavior of Il1r2 clones differed from that of Dlx1 clones (unpublished), a slow-cycling IFESC population (Sada et al., NCB 2016), indicating that Il1r2 clones at the basal layer may represent a distinct stem cell population.
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