Language
Country/Area
No result found
The mystery of TECs: What makes these cells so important in the immune system?
Thymic epithelial cells (TECs) play a key role in the complex architecture of the immune system. These specialized cells are highly anatomically, phenotypically, and functionally heterogeneous and are located in the outer layer (epithelium) of the thymic stroma. As the major lymphoid organ, the thymus is responsible for the development and maturation of T cells. TECs form a unique microenvironment with T cell precursors (thymocytes) at various developmental stages that is essential for the generation of functionally competent T lymphocytes and self-tolerance. Dysfunction of TECs can lead to a variety of immune deficiencies and autoimmune diseases.
The developmental structure and functional arrangement of TECs not only determine the normal functioning of the immune system, but also affect an individual's ability to resist disease.
TECs Grouping
The final anatomical position of the thymus is achieved by fetal age six weeks. TECs are derived from non-hematopoietic cells and are characterized by negative expression of CD45 and positive expression of EpCAM. Based on their phenotype and function, TECs can be subdivided into two groups: cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs). cTECs are located in the outer thymic cortex, while mTECs are located in the inner thymic medulla. Both are involved in maintaining central and peripheral tolerance, with cTECs playing a key role in positive selection and mTECs eliminating self-reactive thymocytes through negative selection.
Maturation process
Maturation of medullary thymic epithelial cells
Maturation of mTEC results in the expression of high levels of MHC II, CD80, the autoimmune regulator Aire, and tissue-specific antigens (TRAs). Mature mTECs will enter a terminal differentiation stage, a process accompanied by the loss of specific maturation factors and the expression of keratin.
Maturation of cortical thymic epithelial cells
The maturation of cTEC is also driven by the high expression of MHC II molecules and is accompanied by the action of multiple proteases. Surface markers of cTECs include Ly51 and CD205, and these cells are considered to be epithelial progenitor cells of the cortex.
The development of TECs
The development of TECs begins with early stage regulation through transcription factors (such as Hoxa3, Pax1/9, Eya1, etc.), among which Foxn1 is an important transcription factor in all stages and plays a key role in the differentiation and function of TECs. Among as many as 400 Foxn1-related genes, many are essential for the development of TECs.
Positive and negative selection of T cells
Positive selection
Double negative (DN) T cells undergo proliferation and differentiation and develop into double positive (DP) stage T cells. During this process, their T cell receptors (TCRs) are tested to recognize self and non-self molecules. Thymocytes that interact well with MHC molecules are able to survive and further develop into CD4- or CD8-positive T cells, depending on the type of MHC molecules encountered.
Negative selection
During negative selection, thymocytes eliminate self-reactive T cells that are overly reactive to self-antigens. During this process, mTECs provide a range of self-peptides to choose from and maintain self-tolerance.
Related diseases
Dysfunction of TECs is associated with a variety of immune diseases, including autoimmune diseases and immunodeficiency. The roots of these disorders are generally traced to defects in the maturation of TECs, leading to attacks on the self. For example, autoimmune thyroiditis or rheumatoid arthritis are caused by the failure of TECs to effectively execute negative selection.
When we think about the role of TECs in the immune system, we can't help but ask: How can these tiny cells influence our health and disease?
