Synchronized development of thymic eosinophils and thymocytes

Author:

Ota Ayami1,Iguchi Takahiro1,Nitta Sachiko1,Muro Ryunosuke1,Mino Nanami1,Tsukasaki Masayuki2,Penninger Josef M3456ORCID,Nitta Takeshi17ORCID,Takayanagi Hiroshi1

Affiliation:

1. Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo , Tokyo 113-0033 , Japan

2. Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo , Tokyo 113-0033 , Japan

3. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) , Vienna , Austria

4. Department of Medical Genetics, Life Sciences Institute, The University of British Columbia , Vancouver, British Columbia , Canada

5. Department of Innovative Organoid Research, Helmholtz Centre for Infection Research , Braunschweig , Germany

6. Eric Kandel Institute, Department of Laboratory Medicine, Medical University Vienna , Vienna ,  Austria

7. Division of Molecular Pathology, Research Institute for Biomedical Sciences, Tokyo University of Science , Chiba 278-0022 , Japan

Abstract

Abstract The thymus is an organ required for T cell development and is also an eosinophil-rich organ; however, the nature and function of thymic eosinophils remain unclear. Here, we characterized the gene expression and differentiation mechanism of thymic eosinophils in mice. Thymic eosinophils showed a distinct gene expression profile compared with other organ-resident eosinophils. The number of thymic eosinophils was controlled by medullary thymic epithelial cells (mTECs). In Rag-deficient mice, the unique gene expression signature of thymic eosinophils was lost but restored by pre-T cell receptor signalling, which induces CD4+ CD8+ thymocyte differentiation, indicating that T cell differentiation beyond the CD4− CD8− stage is necessary and sufficient for the induction of thymic eosinophils. These results demonstrate that thymic eosinophils are quantitatively and qualitatively regulated by mTECs and developing thymocytes, respectively, suggesting that thymic eosinophils are a distinct, thymus-specific cell subset, induced by interactions with thymic cells.

Funder

Japan Society for Promotion of Science

Japan Agency for Medical Research and Development

Publisher

Oxford University Press (OUP)

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