Publications by authors named "Janine Melsen"
Article Synopsis
- Pediatric patients with unexplained bone marrow failure are often diagnosed with aplastic anemia, and since this condition may be auto-immune, immune suppressive therapy is considered, though most severe cases are treated with hematopoietic stem cell transplantation as it offers a cure.
- A study analyzed NK- and B-cells from bone marrow and blood samples of seven pediatric AA patients compared to healthy donors, revealing specific changes in their NK-cell populations and a reduction in B-cell counts.
- The findings suggest that a subset of AA patients with reduced NK-cell function may exhibit auto-immunity, which could contribute to their condition, while transitional B-cells, believed to be regulatory in AA, were also found in lower numbers.
Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells.
View Article and Find Full Text PDFNatural killer (NK) cells develop from CD34+ progenitors in a stage-specific manner defined by changes in cell surface receptor expression and function. Secondary lymphoid tissues, including tonsil, are sites of human NK cell development. Here we present new insights into human NK cell development in pediatric tonsil using cyclic immunofluorescence and imaging mass cytometry.
View Article and Find Full Text PDFHuman natural killer (NK) cells in lymphoid tissues can be categorized into three subsets: CD56CD16, CD56CD16 and CD69CXCR6 lymphoid tissue-resident (lt)NK cells. How the three subsets are functionally and developmentally related is currently unknown. Therefore, we performed single-cell RNA sequencing combined with oligonucleotide-conjugated antibodies against CD56, CXCR6, CD117 and CD34 on fresh bone marrow NK cells.
View Article and Find Full Text PDFThe first successful European hematopoietic stem cell transplantation (HSCT) was performed in 1968 as treatment in a newborn with IL2RG deficiency using an HLA-identical sibling donor. Because of declining naive T and natural killer (NK) cells, and persistent human papilloma virus (HPV)-induced warts, the patient received a peripheral stem cell boost at the age of 37 years. NK and T cells were assessed before and up to 14 years after the boost by flow cytometry.
View Article and Find Full Text PDFAtaxia Telangiectasia (AT) is a rare inherited disorder characterized by progressive cerebellar ataxia, chromosomal instability, cancer susceptibility and immunodeficiency. AT is caused by mutations in the ATM gene, which is involved in multiple processes linked to DNA double strand break repair. Immunologically, ATM mutations lead to hampered V(D)J recombination and consequently reduced numbers of naive B and T cells.
View Article and Find Full Text PDFArticle Synopsis
- Natural killer (NK) cells are a type of innate immune cell important for their ability to attack infected or cancerous cells and are identified by CD56 expression.
- There are two main subsets of human NK cells: CD56 bright (about 10%) and CD56 dim (around 90%), and similar NK-like cells can be created from induced pluripotent stem cells (iPSC).
- A new, simple protocol is introduced for isolating and stimulating these NK cells or NK-like cells, allowing researchers to efficiently measure the secretion of cytokines and chemokines even when starting with a small number of cells.
The introduction of single-cell platforms inspired the development of high-dimensional single-cell analysis tools to comprehensively characterize the underlying cellular heterogeneity. Flow cytometry data are traditionally analyzed by (subjective) gating of subpopulations on two-dimensional plots. However, the increasing number of parameters measured by conventional and spectral flow cytometry reinforces the need to apply many of the recently developed tools for single-cell analysis on flow cytometry data, as well.
View Article and Find Full Text PDFProstate Cancer is the most common cancer and the second leading cause of cancer-related death in males. When prostate cancer acquires castration resistance, incurable metastases, primarily in the bone, occur. The aim of this study is to test the applicability of targeting melanoma cell adhesion molecule (MCAM; CD146) with a mAb for the treatment of lytic prostate cancer bone metastasis.
View Article and Find Full Text PDFArticle Synopsis
- - This study identifies a unique population of natural killer (NK) cells in human lymphoid tissues called CD69CXCR6 lymphoid tissue NK (ltNK) cells, which differ in gene expression and functional characteristics from other NK cell populations.
- - RNA sequencing revealed that ltNK cells show significant differences in 1,353 genes related to migration and cell adhesion molecules compared to circulating NK cells, highlighting their distinct functional roles.
- - The research suggests that ltNK cells are tissue-resident, exhibiting low killing activity and proliferative capacity while displaying similarities in gene expression to memory CD8 T cells, indicating a unique phenotype and potential functional restraint in immune responses.
Article Synopsis
- Two main subsets of human natural killer (NK) cells are identified: CD56(dim)CD16(+) and CD56(bright)CD16(-/+) cells, with the latter being more prevalent in tissues outside the blood.
- CD56(bright) NK cells show significant diversity based on their tissue location, with specific markers indicating their functions in organs like the uterus and liver.
- Understanding the differences between circulating and tissue-resident CD56(bright) NK cells is crucial for comprehending their unique roles in immune regulation.
Article Synopsis
- Human NK cells are primarily studied through blood samples, focusing on conventional CD56(bright) and CD56(dim) types, but a new subset has been identified in lymphoid organs.
- This new NK cell subset, marked by CD69 and CXCR6, makes up 30-60% of NK cells in bone marrow, spleen, and lymph nodes, but is not found in blood.
- The CD69(+)CXCR6(+) NK cells have unique characteristics, such as intermediate CD56 expression and they require activation to unleash their cytotoxic abilities, distinguishing them from conventional NK cells.