Identification of novel thymic epithelial cell subsets whose differentiation is regulated by RANKL and Traf6
| Autor: | Yongwon Choi, Nichole Danzl, Seihwan Jeong, Konstantina Alexandropoulos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Aging
Time Factors T-Lymphocytes Cellular differentiation Immunofluorescence lcsh:Medicine Autoimmunity Epithelial cells Adaptive Immunity Major Histocompatibility Complex Mice Cell differentiation Lymphoid Organs lcsh:Science Multidisciplinary hemic and immune systems Epithelial Cell Adhesion Molecule Cell biology Thymus Thymocyte RANKL Immunotherapy Immunohistochemical Analysis tissues Research Article medicine.medical_specialty Immune Cells Immunology education T cells Antigen-Presenting Cells Mice Transgenic Immunopathology Thymus Gland Thymus--Physiology Biology Models Biological Immune Deficiency Antigens Neoplasm Internal medicine Precursor cell Immune Tolerance medicine Animals Cell Proliferation TNF Receptor-Associated Factor 6 Transplantation Cell growth FOS: Clinical medicine RANK Ligand lcsh:R Immunity Immunologic Subspecialties Mice Inbred C57BL Keratin 5 Endocrinology Animals Newborn Immune System Immunologic Techniques biology.protein Keratin 8 lcsh:Q Cell Adhesion Molecules Biomarkers Gene Deletion CD8 Transcription Factors |
| Zdroj: | PLoS ONE, Vol 9, Iss 1, p e86129 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Thymic epithelial cells (TECs) are critical for the normal development and function of the thymus. Here, we examined the developmental stages of TECs using quantitative assessment of the cortical and medullary markers Keratin 5 and Keratin 8 (K5 and K8) respectively, in normal and gain/loss of function mutant animals. Gain of function mice overexpressed RANKL in T cells, whereas loss of function animals lacked expression of Traf6 in TECs (Traf6ΔTEC). Assessment of K5 and K8 expression in conjunction with other TEC markers in wild type mice identified novel cortical and medullary TEC populations, expressing different combinations of these markers. RANKL overexpression led to expansion of all medullary TECs (mTECs) and enlargement of the thymic medulla. This in turn associated with a block in thymocyte development and loss of CD4+ CD8+, CD4+ and CD8+ thymocytes. In contrast, Traf6 deletion inhibited the production of most TEC populations including cortical TECs (cTECs), defined by absence of UEA-1 binding and LY51 expression, but had no apparent effect on thymocyte development. These results reveal a large degree of heterogeneity within the TEC compartment and the existence of several populations exhibiting concomitant expression of cortical, medullary and epithelial markers and whose production is regulated by RANKL and Traf6. |
| Databáze: | OpenAIRE |
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