Understanding the role of Hassall's body abnormalities in the breakdown of self-tolerance

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H02640
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto University
• Principal Investigator: Hamazaki Yoko 京都大学, iPS細胞研究所, 教授 (10362477)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 胸腺 / 自己寛容 / ハッサル小体

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.

Free Research Field

免疫学

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。