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Purpose Of Review: Cells of the immune system are replaced in large numbers throughout life, and the underlying mechanisms have been extensively studied. Whereas the pace of discovery in this area is unprecedented, many questions remain, particularly with respect to lymphocyte formation.
Recent Findings: While transcription factors have long been a focus of investigation, microRNAs are also being implicated in lymphopoiesis. Lymphocytes are normally replaced in correct proportion to other blood cells, but ratios change dramatically during infections. Long-standing issues relating to T versus B lineage divergence remain but have been enriched with remarkable new findings about thymus seeding. There are indications that at least some age-related changes in lymphopoiesis may be reversible. Finally, knowledge obtained from studies of mice is slowly being extended to humans.
Summary: We can now appreciate that new lymphoid progenitors are drawn from a heterogeneous collection of hematopoietic stem cells through asynchronous patterns of gene expression. Complex interactions then occur between the gene products, preparing lymphoid progenitors to respond to environmental cues. Whereas unique markers describe the process of lymphocyte formation in humans, fundamental information now available should suggest ways to promote rebound from chemotherapy or transplantation and reverse declines associated with aging.
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http://dx.doi.org/10.1097/MOH.0b013e3283612628 | DOI Listing |
J Transl Med
March 2025
Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Background: Zinc is an essential trace element with high importance for immune function. Previous research has shown that vegetarians and vegans are at increased risk of zinc deficiency, due to low zinc bioavailability in plant-based food. However, its effects on immune parameters in healthy adults following these diets remain largely unexplored.
View Article and Find Full Text PDFBlood Res
March 2025
Cancer Research Institute, Seoul National University, Seoul, Korea.
Clonal hematopoiesis (CH), characterized by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations, has emerged as a significant age-related phenomenon with profound implications for human health. While initially recognized in the 1960s, recent technological advances have revealed its complex nature and widespread prevalence, affecting up to 84% of individuals aged ≥ 70 years. The clinical significance of CH extends beyond its well-established role as a precursor to hematological malignancies, encompassing its association with cardiovascular diseases, chronic kidney disease, and other non-malignant disorders.
View Article and Find Full Text PDFAdv Exp Med Biol
March 2025
Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
During the development of T cells in the thymus, differentiating thymocytes move through specific thymic compartments and interact with the cortical and medullary microenvironments of the thymic lobules. This migration is primarily controlled by adhesion molecules, such as extracellular matrix ligands and receptors, and soluble factors like chemokines that are important for thymocyte differentiation. The migration events driven by these molecules include the entry of lymphoid progenitors from the bone marrow, movement within the thymus, and the exit of mature thymocytes.
View Article and Find Full Text PDFAdv Exp Med Biol
March 2025
Department of Cell Biology. Faculty of Biological Sciences, Complutense University of Madrid, Madrid, Spain.
The thymus is a primary lymphoid organ composed of a three-dimensional (3D) epithelial network that provides a specialized microenvironment for the phenotypical and functional maturation of lymphoid progenitors. The specification of the pharyngeal endoderm to thymus fate occurs during the early stages of thymic organogenesis, independent of the expression of the transcription factor Foxn1. However, Foxn1 governs the later organogenesis of thymus together with the colonizing lymphoid cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2025
Children's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
In early postnatal and young adult bone marrow, Leptin receptor-expressing (LepR) stromal cells and endothelial cells synthesize factors required for hematopoietic stem cell (HSC) maintenance, including Stem Cell Factor (SCF) and Cxcl12. However, little is known about how these stromal cells change during aging. We performed single-cell RNA sequencing of mouse bone marrow stromal cells at 2, 12, and 24 mo of age.
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