Understanding the role of Hassall's body abnormalities in the breakdown of self-tolerance
| Project/Area Number |
18H02640
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Hamazaki Yoko 京都大学, iPS細胞研究所, 教授 (10362477)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | 胸腺 / 自己寛容 / ハッサル小体 / 胸腺上皮細胞 / 自己免疫疾患 |
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| Outline of Final Research Achievements |
The thymic medulla is an anatomical region involved in establishing central self-tolerance. Hassall corpuscle (HC) is a characteristic keratinized structure within the thymic medulla; however, the role of HC on central tolerance is not well understood. In this study, we performed gene expression analysis of purified HC-constituting medullary thymic epithelial cells (mTEC). We revealed that HC-mTEC undergo cellular senescence in a steady state and express high levels of inflammatory molecules such as CXCL5 and IL-1 family members. Depletion of neutrophils, which express the CXCL5 receptor, suppresses the activation of pDCs in the thymic medulla. These results suggest that neutrophils are recruited and activated in response to CXCL5 produced as part of SASP from HC mTECs, and he activated neutrophils may induce pDCs activation in the thymic medulla. In summary, we succeeded in defining HC constitutive mTEC at the molecular level.
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| Academic Significance and Societal Importance of the Research Achievements |
HCを構成する髄質上皮細胞を純化し、その遺伝子発現の特徴を明らかにすることで、長らく組織学定義にとどまっていた胸腺髄質のHCを分子レベルで定義することができた。今後、HCの過形成や低形成が胸腺髄質機能の異常制御や中枢性自己寛容の破綻に果たす役割を理解することで、自己免疫疾患発症メカニズムの一端が明らかになることが期待される。
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Report
(5 results)
Research Products
(27 results)
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[Journal Article] Selective expression of claudin-5 in thymic endothelial cells regulates the blood-thymus barrier and T-cell export2021
Author(s)
Takahiro Nagatake, Yan-Chun Zhao, Takeshi Ito, Masahiko Itoh, Kohei Kometani, Mikio Furuse, Azusa Saika, Eri Node, Jun Kunisawa, Nagahiro Minato, Yoko Hamazaki
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Journal Title
International Immunology
Volume: 33(3)
Issue: 3
Pages: 171-182
DOI
Related Report
Peer Reviewed / Open Access
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