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Dendritic cell­-biased precursors support early human thymopoiesis

Intrathymic dendritic cell (DC)-biased precursors act as hematopoietic stromal cells that support the generation of human T cell progenitors from hematopoietic progenitor cells, via crosstalk with immature thymocytes that express TNF receptor 2. This function of DC precursors can be exploited to generate T cell precursors and competent T cells for cell therapy.

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Fig. 1: lntrathymic tmTNF–TNFR2-mediated cellular crosstalk supports early human T cell development and can be mimicked in vitro.

References

  1. Moirangthem, R. D. et al. A DL-4- and TNFα­ based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors. Cell, Mol lmmunol 18, 1662–1676 (2021). This paper reports the use of sTNF to generate human T cell progenitors.

    Article  CAS  Google Scholar 

  2. Lavaert, M. et al. Integrated scRNA-seq identifies human postnatal thymus seeding progenitors and regulatory dynamics of differentiating immature thymocytes. Immunity 52, 1088–1104 (2020). This paper reports the two types of thymus seeding progenitor cells in human postnatal thymus.

    Article  CAS  PubMed  Google Scholar 

  3. Edgar, J. M. et al. Multi-objective optimization reveals time- and dose-dependent inflammatory cytokine-mediated regulation of human stem cell derived T-cell development. NPJ Regen. Med. 7, 11 (2022). This paper reports sTNF as a stage-specific and dose -specific enhancer of T cell-lineage differentiation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Seel, C. S. et al. Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids. Nat. Methods 14, 521–530 (2021). This paper establishes an organoid system for three-dimensional in vitro modelling of T cell development.

    Google Scholar 

  5. Fischer, R. et al. Selective targeting of TNF Receptors as a novel therapeutic approach. Front. Cell Dev. Biol. 8, 401 (2020). This review article discusses the differential roles of the two TNF receptors and their selective targeting.

    Article  PubMed  PubMed Central  Google Scholar 

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This is a summary of: Liang, K. L. et al. Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF. Nat. Immunol. https://doi.org/10.1038/s41590-022-01417-6 (2023).

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Dendritic cell­-biased precursors support early human thymopoiesis. Nat Immunol 24, 389–390 (2023). https://doi.org/10.1038/s41590-023-01421-4

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