The proprotein convertase furin regulates the development of thymic epithelial cells to ensure central immune tolerance.

The generation of mature T cells and establishment of central tolerance is predominantly orchestrated by thymic epithelial cells (TECs). Proprotein convertases are responsible for the proteolysis of proproteins into their mature bioactive counterparts. Here, we found that , a member of the subtilisin/kexin-like PCs family, is highly expressed in TECs compared with other members of this family.

Absence of TSC1 Accelerates CD8 T cell-mediated Acute Cardiac Allograft Rejection.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by inactivating mutations in or .Patients with TSC often require organ transplantation after organ failure. TSC1 serves as an important control node in immune cell development and responses; however, its effect on T cells in transplant immunity has not yet been explored.

Trappc1 deficiency impairs thymic epithelial cell development by breaking endoplasmic reticulum homeostasis.

Thymic epithelial cells (TECs) are important for T cell development and immune tolerance establishment. Although comprehensive molecular regulation of TEC development has been studied, the role of transport protein particle complexes (Trappcs) in TECs is not clear. Using TEC-specific homozygous or heterozygous Trappc1 deleted mice model, we find that Trappc1 deficiency cause severe thymus atrophy with decreased cell number and blocked maturation of TECs.

Age-related thymic involution: Mechanisms and functional impact.

The thymus is the primary immune organ responsible for generating self-tolerant and immunocompetent T cells. However, the thymus gradually involutes during early life resulting in declined naïve T-cell production, a process known as age-related thymic involution. Thymic involution has many negative impacts on immune function including reduced pathogen resistance, high autoimmunity incidence, and attenuated tumor immunosurveillance.

Cytosolic Nuclear Sensor Dhx9 Controls Medullary Thymic Epithelial Cell Differentiation by p53-Mediated Pathways.

Thymic epithelial cells (TECs) critically participate in T cell maturation and selection for the establishment of immunity to foreign antigens and immune tolerance to self-antigens of T cells. It is well known that many intracellular and extracellular molecules elegantly have mastered the development of medullary TECs (mTECs) and cortical TECs (cTECs). However, the role played by NTP-dependent helicase proteins in TEC development is currently unclear.

Sirt6-mediated epigenetic modification of DNA accessibility is essential for Pou2f3-induced thymic tuft cell development.

Thymic epithelial cells (TECs) are essential for the production of self-tolerant T cells. The newly identified thymic tuft cells are regulated by Pou2f3 and represent important elements for host type 2 immunity. However, epigenetic involvement in thymic tuft cell development remains unclear.

The Development and Survival of Thymic Epithelial Cells Require TSC1-Dependent Negative Regulation of mTORC1 Activity.

Thymic epithelial cells (TECs) are critical for the development and generation of functionally competent T cells. Until now, the mechanism that regulates the survival of TECs is poorly understood. In the current study, we found that controls the homeostasis of medullary TECs (mTECs) by inhibiting lysosomal-mediated apoptosis pathway in mice.

Regulates the Development of Medullary Thymic Epithelial Cells and Contributes to the Establishment of Central Immune Tolerance.

Although some advances have been made in understanding the molecular regulation of mTEC development, the role of epigenetic regulators in the development and maturation of mTEC is poorly understood. Here, using the TEC-specific knockout mice, we found the deacetylase Sirtuin 6 () is essential for the development of functionally competent mTECs. First of all, TEC-specific deletion dramatically reduces the mTEC compartment, which is caused by reduced DNA replication and subsequent impaired proliferation ability of -deficient mTECs.

CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF-κB signaling pathway.

Thymic epithelial cells (TECs) are indispensable for T cell development, T cell receptor (TCR) repertoire selection, and specific lineage differentiation. Medullary thymic epithelial cells (mTECs), which account for the majority of TECs in adults, are critical for thymocyte selection and self-tolerance. CD74 is a nonpolymorphic transmembrane glycoprotein of major histocompatibility complex class II (MHCII) that is expressed in TECs.

mTORC2 negatively controls the maturation process of medullary thymic epithelial cells by inhibiting the LTβR/RANK-NF-κB axis.

The differentiation of mature medullary thymic epithelial cells (mTECs) is critical for the induction of central immune tolerance. Although the critical effect of mechanistic target of rapamycin complex 1 (mTORC1) in shaping mTEC differentiation has been studied, the regulatory role of mTORC2 in the differentiation and maturation of mTECs is poorly understood. We herein reported that TEC-specific ablation of a rapamycin-insensitive companion of mTOR (RICTOR), a key component of mTORC2, significantly decreased the thymus size and weight, the total cell number of TECs, and the cell number of mTECs with a smaller degree of reduced cortical thymic epithelial cells.

Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development.

The thymus is the primary lymphoid organ responsible for the generation and maturation of T cells. Thymic epithelial cells (TECs) account for the majority of thymic stromal components. They are further divided into cortical and medullary TECs based on their localization within the thymus and are involved in positive and negative selection, respectively.

Molecular regulatory networks of thymic epithelial cell differentiation.

Functional mature T cells are generated in the thymus. Thymic epithelial cells (TECs) provide the essential microenvironment for T cell development and maturation. According to their function and localization, TECs are roughly divided into cortical TECs (cTECs) and medullary TECs (mTECs), which are responsible for positive and negative selection, respectively.

MTOR signaling is essential for the development of thymic epithelial cells and the induction of central immune tolerance.

Thymic epithelial cells (TECs) are critical for the establishment and maintenance of appropriate microenvironment for the positive and negative selection of thymocytes and the induction of central immune tolerance. Yet, little about the molecular regulatory network on TEC development and function is understood. Here, we demonstrate that MTOR (mechanistic target of rapamycin [serine/threonine kinase]) is essential for proper development and functional maturation of TECs.

Impact of aging immune system on neurodegeneration and potential immunotherapies.

The interaction between the nervous and immune systems during aging is an area of avid interest, but many aspects remain unclear. This is due, not only to the complexity of the aging process, but also to a mutual dependency and reciprocal causation of alterations and diseases between both the nervous and immune systems. Aging of the brain drives whole body systemic aging, including aging-related changes of the immune system.

FSP1(+) fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells.

Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined.