Selective involution of thymic medulla by cyclosporine A with a decrease of mature thymic epithelia, XCR1+ dendritic cells, and epithelium-free areas containing Foxp3+ thymic regulatory T cells
| Autor: | Nobuko Tokuda, Kenjiro Matsuno, Yusuke Kitazawa, Yasushi Sawanobori, Hisashi Ueta |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Histology T cell Injections Subcutaneous Recent Thymic Emigrant Thymus Gland Major histocompatibility complex T-Lymphocytes Regulatory 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Thymic structure medicine Animals Involution (medicine) Molecular Biology Medulla Thymic epithelial cells Original Paper Thymocytes biology Chemistry Immunosuppressive drug Optical Imaging FOXP3 Epithelial Cells Forkhead Transcription Factors Cell Biology Regulatory T cells Dendritic Cells Immunohistochemistry Epithelium Cell biology Thymus Rats Medical Laboratory Technology 030104 developmental biology medicine.anatomical_structure Rats Inbred Lew biology.protein Cyclosporine Receptors Chemokine Immunosuppressive Agents 030215 immunology |
| Zdroj: | Histochemistry and Cell Biology |
| ISSN: | 1432-119X 0948-6143 |
| Popis: | Immunosuppressive drugs such as cyclosporine A (CSA) can disrupt thymic structure and functions, ultimately inducing syngeneic/autologous graft-versus-host disease together with involuted medullas. To elucidate the effects of CSA on the thymus more precisely, we analyzed the effects of CSA on the thymus and T cell system using rats. In addition to confirming the phenomena already reported, we newly found that the proportion of recent thymic emigrants also greatly decreased, suggesting impaired supply. Immunohistologically, the medullary thymic epithelial cells (mTECs) presented with a relative decrease in the subset with a competent phenotype and downregulation of class II major histocompatibility complex molecules. In control rats, thymic dendritic cells (DCs) comprised two subsets, XCR1+SIRP1α−CD4− and XCR1−SIRP1α+CD4+. The former had a tendency to selectively localize in the previously-reported epithelium-containing areas of the rat medullas, and the number was significantly reduced by CSA treatment. The epithelium-free areas, another unique domains in the rat medullas, contained significantly more Foxp3+ thymic Tregs. With CSA treatment, the epithelium-free areas presented strong involution, and the number and distribution of Tregs in the medulla were greatly reduced. These results suggest that CSA inhibits the production of single-positive thymocytes, including Tregs, and disturbs the microenvironment of the thymic medulla, with a decrease of the competent mTECs and disorganization of epithelium-free areas and DC subsets, leading to a generation of autoreactive T cells with selective medullary involution. |
| Databáze: | OpenAIRE |
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