Abstract
The immune system’s ability to resist the invasion of foreign pathogens and the tolerance to self-antigens are primarily centered on the efficient functions of the various subsets of T lymphocytes. As the primary organ of thymopoiesis, the thymus performs a crucial role in generating a self-tolerant but diverse repertoire of T cell receptors and peripheral T cell pool, with the capacity to recognize a wide variety of antigens and for the surveillance of malignancies. However, cells in the thymus are fragile and sensitive to changes in the external environment and acute insults such as infections, chemo- and radiation-therapy, resulting in thymic injury and degeneration. Though the thymus has the capacity to self-regenerate, it is often insufficient to reconstitute an intact thymic function. Thymic dysfunction leads to an increased risk of opportunistic infections, tumor relapse, autoimmunity, and adverse clinical outcome. Thus, exploiting the mechanism of thymic regeneration would provide new therapeutic options for these settings. This review summarizes the thymus’s development, factors causing thymic injury, and the strategies for improving thymus regeneration.
Highlights
The thymus is the primary lymphoid organ for T lymphocyte development and maturation that mediates immune defense against foreign antigens, immune tolerance to self-antigens, and immune surveillance on tumor cells [1]
While mTECs regulate the migration of positively selected thymocytes from the cortex into the medulla via Abbreviations: TECs, thymic epithelial cells; CCL, chemokine ligands; Allo-HCT, Allogeneic hematopoietic cell transplantation; KGF, keratinocyte growth factor; RANK, receptor activator of NF-kB; TEPC, thymic epithelial progenitor cells; TSC, thymic stromal cells; Epidermal growth factor receptor (EGF), epidermal growth factor receptor; FGFR, fibroblast growth factor receptor; fork-head box protein-N1 (FOXN1), forkhead box protein-N1; autoimmune regulatory gene (AIRE), autoimmune regulator
Once the medulla has reached its normal cellularity in the postnatal thymus, the differentiation potential of b5t+ precursors to the mTEC lineage is markedly restricted [33].Of note, studies using b5t-deficient mice showed a significant decline in the number of CD8+ SP thymocytes in the thymic architecture with subsequent altered immune responses, suggesting that the thymoproteasome is essential for the production of self-antigens involved in the positive selection of functional CD4−CD8+ T cells [34].Another transcription factor, ThPOK, has recently been identified to promote CD4+ versus CD8+ lineage divergence and is implicated to be necessary for determining CD4+ helper fate on T cell antigen receptor (TCR)-signaled thymocytes and conservation of CD4+ and regulatory T (Treg) cells and agonist-selected lineage gene programs [35]
Summary
Maxwell Duah 1,2†, Lingling Li 1,2†, Jingyi Shen 1,2, Qiu Lan 1,2, Bin Pan 1,2* and Kailin Xu 1,2*. Reviewed by: Sinead Kinsella, Fred Hutchinson Cancer Research Center, United States. The immune system’s ability to resist the invasion of foreign pathogens and the tolerance to self-antigens are primarily centered on the efficient functions of the various subsets of T lymphocytes. As the primary organ of thymopoiesis, the thymus performs a crucial role in generating a self-tolerant but diverse repertoire of T cell receptors and peripheral T cell pool, with the capacity to recognize a wide variety of antigens and for the surveillance of malignancies. Though the thymus has the capacity to selfregenerate, it is often insufficient to reconstitute an intact thymic function. This review summarizes the thymus’s development, factors causing thymic injury, and the strategies for improving thymus regeneration
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