Background: Thymic stromal derived lymphopoietin (TSLP) is preferentially and highly expressed in the thymus, but its function in T cell development is not clear.
Results: We report here that TSLP, independently or in combination with IL-7, enhances thymopoiesis in the murine fetal thymic organ culture (FTOC) model. Furthermore, TSLP preferentially increases the number and proliferation of the (DN1 and DN2) pro-T progenitor cells, and FTOC lobes from TSLP receptor-null mice show a decreased number of these cells. Finally, DN1-DN2 cells expanded with TSLP in vitro are functional T progenitors that are able to differentiate into mature T cells in fetal or adult thymus organs.
Conclusion: Together, these data suggest that TSLP plays an important role in expansion of thymocyte progenitors and may be of value for expanding T progenitor cells in vitro.
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http://dx.doi.org/10.1186/1471-2172-8-11 | DOI Listing |
Nature
November 2024
Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK.
T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation and selection. In humans, this process starts in early fetal development and is highly active until thymic involution in adolescence. To map the microanatomical underpinnings of this process in pre- and early postnatal stages, we established a quantitative morphological framework for the thymus-the Cortico-Medullary Axis-and used it to perform a spatially resolved analysis.
View Article and Find Full Text PDFFront Immunol
November 2024
Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia.
Blood Adv
November 2024
Institut Necker des Enfantes Malades, PARIS, France.
Alterations inactivating the tumor suppressor gene PTEN drive the development of solid and hematological cancers, such as T-cell acute lymphoblastic leukemia (T-ALL), whereby PTEN loss defines poor-prognosis patients. We investigated the metabolic rewiring induced by PTEN loss in T-ALL, aiming at identifying novel metabolic vulnerabilities. We showed that the enzyme ATP citrate lyase (ACLY) is strictly required for the transformation of thymic immature progenitors and for the growth of human T-ALL, which remain dependent on ACLY activity even upon transformation.
View Article and Find Full Text PDFAdv Exp Med Biol
November 2024
Center for Immunology and Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Thymus is an important primary lymphoid organ for T cell development. After T-lineage commitment, the early thymic progenitors (ETPs) develop into CD4-CD8- (DN), CD4+CD8+ (DP) and further CD4+ SP or CD8+ SP T cells. Under the help of thymic epithelial cells (TEC), dendritic cell (DC), macrophage, and B cells, ETPs undergo proliferation, T cell receptor (TCR) rearrangement, β-selection, positive selection, and negative selection, and thus leading to the generation of T cells that are diverse repertoire immunocompetent but not self-reactive.
View Article and Find Full Text PDFJ Vis Exp
October 2024
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064;
Generation of a functional and self-tolerant T cell repertoire is a complex process dependent on the thymic microenvironment and, primarily, on the properties of its extracellular matrix (ECM). Thymic epithelial cells (TECs) are crucial in thymopoiesis, nurturing and selecting developing T cells by filtering self-reactive clones. TECs have been empirically demonstrated to be particularly sensitive to physical and chemical clues supplied by the ECM and classical monolayer cell culture leads to a quick loss of functionality until their death.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!