Steven Strubbe

All Publications

• In Vitro Model Systems to Study Human T Cell Development. Methods in molecular biology (Clifton, N.J.) Lambrechts, N., Liang, K. L., Velghe, I., Strubbe, S., Dolens, A., Taghon, T. 2023; 2580: 335-354

  Abstract

  Not only is human T cell development characterized by unique changes in surface marker expression, but it also requires specific growth factors and conditions to mimic and study T cell development in vitro. In this chapter, we provide an overview of the specific aspects that need attention when performing T cell differentiation cultures with human hematopoietic and T cell progenitors.

  View details for DOI 10.1007/978-1-0716-2740-2_21

  View details for PubMedID 36374468

• Type 1 regulatory T cell-mediated tolerance in health and disease. Frontiers in immunology Freeborn, R. A., Strubbe, S., Roncarolo, M. G. 2022; 13: 1032575

  Abstract

  Type 1 regulatory T (Tr1) cells, in addition to other regulatory cells, contribute to immunological tolerance to prevent autoimmunity and excessive inflammation. Tr1 cells arise in the periphery upon antigen stimulation in the presence of tolerogenic antigen presenting cells and secrete large amounts of the immunosuppressive cytokine IL-10. The protective role of Tr1 cells in autoimmune diseases and inflammatory bowel disease has been well established, and this led to the exploration of this population as a potential cell therapy. On the other hand, the role of Tr1 cells in infectious disease is not well characterized, thus raising concern that these tolerogenic cells may cause general immune suppression which would prevent pathogen clearance. In this review, we summarize current literature surrounding Tr1-mediated tolerance and its role in health and disease settings including autoimmunity, inflammatory bowel disease, and infectious diseases.

  View details for DOI 10.3389/fimmu.2022.1032575

  View details for PubMedID 36389662

• PHF6 Expression Levels Impact Human Hematopoietic Stem Cell Differentiation FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY Loontiens, S., Dolens, A., Strubbe, S., van de Walle, I., Moore, F. E., Depestel, L., Vanhauwaert, S., Matthijssens, F., Langenau, D. M., Speleman, F., Van Vlierberghe, P., Durinck, K., Taghon, T. 2020; 8: 599472

  Abstract

  Transcriptional control of hematopoiesis involves complex regulatory networks and functional perturbations in one of these components often results in malignancies. Loss-of-function mutations in PHF6, encoding a presumed epigenetic regulator, have been primarily described in T cell acute lymphoblastic leukemia (T-ALL) and the first insights into its function in normal hematopoiesis only recently emerged from mouse modeling experiments. Here, we investigated the role of PHF6 in human blood cell development by performing knockdown studies in cord blood and thymus-derived hematopoietic precursors to evaluate the impact on lineage differentiation in well-established in vitro models. Our findings reveal that PHF6 levels differentially impact the differentiation of human hematopoietic progenitor cells into various blood cell lineages, with prominent effects on lymphoid and erythroid differentiation. We show that loss of PHF6 results in accelerated human T cell development through reduced expression of NOTCH1 and its downstream target genes. This functional interaction in developing thymocytes was confirmed in vivo using a phf6-deficient zebrafish model that also displayed accelerated developmental kinetics upon reduced phf6 or notch1 activation. In summary, our work reveals that appropriate control of PHF6 expression is important for normal human hematopoiesis and provides clues towards the role of PHF6 in T-ALL development.

  View details for DOI 10.3389/fcell.2020.599472

  View details for Web of Science ID 000589966600001

  View details for PubMedID 33251223

  View details for PubMedCentralID PMC7672048