DROSHA but not DICER is required for human haematopoietic stem cell function.

Objectives: DROSHA and DICER have central roles in the biogenesis of microRNAs (miRNAs). However, we previously showed that in the murine system, DROSHA has an alternate function where it directly recognises and cleaves protein-coding messenger (m)RNAs and this is critical for safeguarding the pluripotency of haematopoietic stem cells (HSCs). Maintenance of murine HSC function is dependent on DROSHA-mediated cleavage of two mRNAs, and .

Synthetic hookworm-derived peptides are potent modulators of primary human immune cell function that protect against experimental colitis in vivo.

The prevalence of autoimmune diseases is on the rise globally. Currently, autoimmunity presents in over 100 different forms and affects around 9% of the world's population. Current treatments available for autoimmune diseases are inadequate, expensive, and tend to focus on symptom management rather than cure.

Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141 dendritic cells to activate naïve and memory NY-ESO-1-specific CD8 T cells.

Background: Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8 T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141 DCs, the human cDC1 equivalent. CD141 DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8 T cell responses.

Simple, rapid and inexpensive typing of common HLA class I alleles for immunological studies.

Current HLA-typing methods are typically designed to provide exquisitely-detailed identification of multiple HLA-alleles to satisfy the requirements for organ and bone marrow transplantation or genetic studies. Many human immunological studies, on the other hand, focus around only a small number of HLA alleles that are abundant or of relevance to specific diseases. Consequently, for such studies, many HLA typing approaches are not cost-effective and are potentially complicated, slow and not easily performed in-house.

Activation of human CD141 and CD1c dendritic cells in vivo with combined TLR3 and TLR7/8 ligation.

Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141 and CD1c myeloid and CD123 plasmacytoid dendritic cells (DC) develop from human cord blood CD34 cells in immunodeficient mice. CD141 DC are the human equivalents of murine CD8 /CD103 DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte responses, making them attractive targets to exploit for the development of new cancer immunotherapies.

Influenza nucleoprotein DNA vaccination by a skin targeted, dry coated, densely packed microprojection array (Nanopatch) induces potent antibody and CD8(+) T cell responses.

DNA vaccines have many advantages such as thermostability and the ease and rapidity of manufacture; for example, in an influenza pandemic situation where rapid production of vaccine is essential. However, immunogenicity of DNA vaccines was shown to be poor in humans unless large doses of DNA are used. If a highly efficacious DNA vaccine delivery system could be identified, then DNA vaccines have the potential to displace protein vaccines.

Colocalization of cell death with antigen deposition in skin enhances vaccine immunogenicity.

Vaccines delivered to the skin by microneedles-with and without adjuvants-have increased immunogenicity with lower doses than standard vaccine delivery techniques such as intramuscular or intradermal injection. However, the mechanisms underlying this skin-mediated "adjuvant" effect are not clear. Here, we show that the dynamic application of a microprojection array (the Nanopatch) to skin generates localized transient stresses invoking cell death around each projection.