Two separate groups of researchers have reported large-scale genomic studies of blood cells that captured much of the variation predisposing blood cells to both common and rare diseases. One study, led by investigators at the University of Wisconsin at Milwaukee and the University of Montreal, conducted a meta-analysis of studies involving nearly 750,000 individuals, including nearly 200,000 that were not of European ancestry – a much-needed boost for genomic diversity in GWAS. The team identified genomic variants related to a total of 15 traits in white blood cells, red blood cells and platelets. They identified a total of more than 5,500 trait-related variants. By using their multi-ethnic approach, they were able to identify nearly 100 trait-related genetic variants that were not found in the European ancestry group. The researchers concluded that “our results for hematological traits highlight the value of a more global representation of populations in genetic studies.” The second study, which was conducted exclusively on samples from the UK Biobank, identified new variants in individuals of European ancestry only. The papers appeared back to back in the Sept. 3, 2020, issue of Cell.
Teaching T cells restraint
Researchers at the University of Massachusetts at Amherst have developed an intracellularly acting antibody that facilitated the development of T cells into regulatory T cells by inhibiting protein kinase C theta PKCθ). Regulatory T cells are a subset of T cells that suppresses the immune response, and their presence is critical for preventing autoimmunity and, after bone marrow transplantation, graft-vs.-host-disease. PKCθ is critical for turning T cells into effector T cells, as it links antigen stimulation with co-stimulatory signals in the immunological synapse between T cells and antigen-presenting cells. The researchers demonstrated that by blocking PKCθ via a cell-penetrating antibody, they were able to bias the fate of primary human T cells toward regulatory T cells. When administered at the time of graft-vs.-host disease induction, using a humanized mouse model, regulatory T cells were superior to non-treated T cells in attenuating lethal outcomes, the authors wrote. “This antibody delivery approach may overcome obstacles currently encountered using patient-derived regulatory T cells as a cell-based therapy for immune modulation. They published their study in the Sept. 2, 2020, issue of Molecular Therapy.