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The miracle of cell differentiation: Why do cTEC and mTEC have such different functions?
In the operation of the immune system, the role of the thymus cannot be ignored. This major lymphoid organ located in the thymus is mainly responsible for the development and maturation of T cells. Among them, thymic epithelial cells (TECs) are particularly critical because they constitute the main component of the thymic microenvironment. However, TECs are not a single type of cell; they can be subdivided into two different types: cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs). There are significant differences in functions, characteristics and developmental pathways between the two, which has aroused the curiosity of scientists. What factors make these cells unique in their roles?
Thymic epithelial cells are one of the most important cell types in the thymus. They are not only crucial for the development of T cells, but also an important supporter of self-tolerance.
The role and organizational structure of TECs
TECs are specialized cells located in the outer layer of the thymic stroma and are highly anatomical, phenotypic and functionally heterogeneous. The microenvironment of the thymus consists of a network of TECs and thymocytes (T cell precursors) at different developmental stages. cTECs are located in the outer cortex of the thymus, while mTECs are located in the inner medulla. A major difference between the two types of cells is their role in T cell selection. cTECs are primarily involved in positive selection, promoting the development of harmless T cells, whereas mTECs eliminate self-reactive thymocytes in negative selection.
The process of cell differentiation
The development of TECs begins with complex interactions with multiple factors such as transplantation, genetics, and transcription factors. During the development of all TECs, Foxn1 is a critical transcription factor that controls the expression of more than 400 specific genes related to the differentiation and function of TECs. For cTECs, early development requires highly expressed Pax 1/9, Six1/4 and Hoxa3, while the development of mTECs depends on Relb and NFκB signaling, but does not require the participation of Foxn1.
Positive filtering and negative filtering
Positive screening
During the positive screening process, double-negative (DN) T cells proliferate and develop, eventually becoming double-positive (DP) stage T cells. If these T cells can effectively recognize self and non-self molecules after detection with MHC molecules expressed by cTEC, they will survive and differentiate into single-positive (SP) T cells.
Negative filtering
However, without effective negative selection, T cells in the thymus may not respond appropriately to self-antigens, leading to the development of autoimmune diseases. In this process, mTECs promote self-tolerance by expressing a broad range of self-peptides and eliminate T cells reactive to self-tissue.
Abnormalities and diseases of TECs
The dysfunction of TECs may lead to a variety of immune deficiencies and autoimmune diseases. For example, mutations in the Aire gene can lead to the destruction of self-tolerance, leading to a variety of autoimmune diseases, such as autoimmune thyroiditis and type 1 diabetes. The core of these diseases lies in the dysfunction of thymic epithelial cells, which significantly affects the establishment and maintenance of self-tolerance.
Summary
TECs play a crucial role in T cell development, especially in positive and negative selection. Although cTECs and mTECs come from the same source, their functional characteristics and developmental pathways are different, leading to their different roles in the immune system. This differentiation process is full of mystery and deserves our in-depth exploration. When discussing these cells, we cannot help but wonder: What important implications does the uniqueness of these cells provide for our understanding of the immune system?
