Checkpoints in the development of thymic cortical epithelial cells.
In the thymus, interactions between immature thymocytes and thymic epithelial cells (TECs) regulate the development and selection of self-tolerant MHC-restricted T cells. Despite the importance of cortical (cTEC) and medullary (mTEC) thymic epithelial cells in fostering T cell production, events in TEC development are still unclear. Although precursor-product relationships during mTEC development have been reported, and some genetic regulators of mTEC development have been identified, stages in cTEC development occurring downstream of recently identified bipotent cTEC/mTEC progenitors remain poorly defined. In this study, we combine analysis of differentiation, proliferation, and gene expression of TECs in the murine thymus, that has enabled us to identify cTEC progenitors, define multiple stages in cTEC development, and identify novel checkpoints in development of the cTEC lineage. We show an essential requirement for FoxN1 in the initial development of cTEC from bipotent progenitors, and demonstrate a stage-specific requirement for CD4(-)8(-) thymocytes in later stages of cTEC development. Collectively, our data establish a program of cTEC development that should provide insight into the formation and function of the thymic cortex for T cell development.
Shakib
Saba
S
Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, United Kingdom.
Desanti
Guillaume E
GE
Jenkinson
William E
WE
Parnell
Sonia M
SM
Jenkinson
Eric J
EJ
Anderson
Graham
G
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000276:immunology* / Q000378:metabolism
D000949:Histocompatibility Antigens Class II