Developmentally regulated availability of RANKL and CD40 ligand reveals distinct mechanisms of fetal and adult cross-talk in the thymus medulla
T cell tolerance in the thymus is a key step in shaping the developing T cell repertoire. Thymic medullary epithelial cells play multiple roles in this process, including negative selection of autoreactive thymocytes, influencing thymic dendritic cell positioning, and the generation of Foxp3(+) regulatory T cells. Previous studies show that medullary thymic epithelial cell (mTEC) development involves hemopoietic cross-talk, and numerous TNFR superfamily members have been implicated in this process. Whereas CD40 and RANK represent key examples, interplay between these receptors, and the individual cell types providing their ligands at both fetal and adult stages of thymus development, remain unclear. In this study, by analysis of the cellular sources of receptor activator for NF-κB ligand (RANKL) and CD40L during fetal and adult cross-talk in the mouse, we show that the innate immune cell system drives initial fetal mTEC development via expression of RANKL, but not CD40L. In contrast, cross-talk involving the adaptive immune system involves both RANKL and CD40L, with analysis of distinct subsets of intrathymic CD4(+) T cells revealing a differential contribution of CD40L by conventional, but not Foxp3(+) regulatory, T cells. We ...Continue Reading
Disorganization and restoration of thymic medullary epithelial cells in T cell receptor-negative scid mice: evidence that receptor-bearing lymphocytes influence maturation of the thymic microenvironment
Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization
Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR
Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity
Transfection and ligation of CD40 in human oral keratinocytes affect proliferation, adhesion and migration but not apoptosis in vitro
Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin
Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells
RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla
Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input
The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance
The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator
Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity
Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment
Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance
The impact of cell re-entry into the primary lymphoid organs on lymphocyte repertoire and functionality
Lymphotoxin signals from positively selected thymocytes regulate the terminal differentiation of medullary thymic epithelial cells
Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development
Receptor activator of NF-kappaB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit
Lymphotoxin signal promotes thymic organogenesis by eliciting RANK expression in the embryonic thymic stroma
Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance
Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium
Mesenchymal cells regulate retinoic acid receptor-dependent cortical thymic epithelial cell homeostasis
T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction
Conditioned deletion of ephrinB1 and/or ephrinB2 in either thymocytes or thymic epithelial cells alters the organization of thymic medulla and favors the appearance of thymic epithelial cysts
Loss of thymic innate lymphoid cells leads to impaired thymopoiesis in experimental graft-versus-host disease.
RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation
Cutting edge: Antigen-specific thymocyte feedback regulates homeostatic thymic conventional dendritic cell maturation
An essential role for medullary thymic epithelial cells during the intrathymic development of invariant NKT cells
Dynamic changes in epithelial cell morphology control thymic organ size during atrophy and regeneration
Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development.
Phosphatase Wip1 is essential for the maturation and homeostasis of medullary thymic epithelial cells in mice
Osteoprotegerin-Mediated Homeostasis of Rank+ Thymic Epithelial Cells Does Not Limit Foxp3+ Regulatory T Cell Development
Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling
Cultured Human Thymic-Derived Cells Display Medullary Thymic Epithelial Cell Phenotype and Functionality
Role of the thymus in spontaneous development of a multi-organ autoimmune disease in human immune system mice.
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