Vipin Narang

Bio: Vipin Narang is an academic researcher from Singapore Immunology Network. The author has contributed to research in topics: Devanagari & Gene regulatory network. The author has an hindex of 10, co-authored 15 publications receiving 513 citations. Previous affiliations of Vipin Narang include Agency for Science, Technology and Research.

IgG1 memory B cells keep the memory of IgE responses.

Abstract: The unique differentiation of IgE cells suggests unconventional mechanisms of IgE memory. IgE germinal centre cells are transient, most IgE cells are plasma cells, and high affinity IgE is produced by the switching of IgG1 cells to IgE. Here we investigate the function of subsets of IgG1 memory B cells in IgE production and find that two subsets of IgG1 memory B cells, CD80+CD73+ and CD80-CD73-, contribute distinctively to the repertoires of high affinity pathogenic IgE and low affinity non-pathogenic IgE. Furthermore, repertoire analysis indicates that high affinity IgE and IgG1 plasma cells differentiate from rare CD80+CD73+ high affinity memory clones without undergoing further mutagenesis. By identifying the cellular origin of high affinity IgE and the clonal selection of high affinity memory B cells into the plasma cell fate, our findings provide fundamental insights into the pathogenesis of allergies, and on the mechanisms of antibody production in memory B cell responses.IgE is an important mediator of protective immunity as well as allergic reaction, but how high affinity IgE antibodies are produced in memory responses is not clear. Here the authors show that IgE can be generated via class-switch recombination in IgG1 memory B cells without additional somatic hypermutation.

Functionally diverse human T cells recognize non-microbial antigens presented by MR1

Abstract: White blood cells called T cells recognize germs and infected cells, and get rid of other cells in the body that look different to healthy cells – for example, tumor cells. These activities all depend on a molecule called the T cell receptor (or TCR for short), which is found on the surface of the T cells. Each TCR interacts with a specific complex on the surface of the target cell. One of the molecules recognized by the TCR is known as MHC class I-related (shortened to MR1). This molecule attracts TCRs to infected cells, but it was not know if the MR1 molecule could attract TCRs to cancer cells too. Lepore et al. now show that there are indeed T cells in humans that recognize cancer cells through interaction with the MR1 molecules produced by the cancer cells. This new group of T cells has been named MR1T, and the cells can be easily detected in the blood of healthy individuals. The cells can be classified as a new cell population based on their capacity to recognize MR1 and how they react with different types of cancer cells. Importantly, the MR1 that attracts these TCRs is the same in all people, and so the same TCR may recognize MR1-expressing cancer cells from different patients. The next challenge is to identify MR1T cells that recognize and kill cancer cells from different tissues. These studies will hopefully pave the way for new and broader strategies to combat cancer.

Systemic and Metabolic Signature of Sarcopenia in Community-Dwelling Older Adults.

Abstract: BACKGROUND Evidence suggests the pivotal contribution of nutrition as a modifiable risk factor for sarcopenia. The present cross-sectional study characterized the nutritional and metabolic profile of sarcopenia through an extensive exploration of a wide array of blood biomarkers related to muscle protein metabolism and transcriptomic signatures in community-dwelling elderly adults. METHODS Among 189 older individuals with a mean age of 73.2 years, sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia criteria based on appendicular lean mass measured by dual-energy X-ray absorptiometry scan, muscle strength, and gait speed. Nutritional status was evaluated using the mini-nutritional assessment (MNA). In addition, we assessed specific blood biomarkers of nutritional status (plasma essential amino acids [EAAs], vitamins), nicotine-derived metabolites, and an extensive microarray analysis from peripheral blood mononuclear cells. RESULTS Malnutrition defined by low MNA score was independently associated with sarcopenia (p < .001). Sarcopenic elderly showed lower body mass index and leptin and higher adiponectin and high-density lipoproteins. Levels of EAAs including lysine, methionine, phenylalanine, threonine, as well as branched-chain AAs and choline, were inversely associated with sarcopenia. Furthermore, nicotine metabolites (cotinine and trans-3'-hydroxycotine) and vitamin B6 status were linked to one or more clinical and functional measures of sarcopenia. Differentially expressed genes and ingenuity pathway analysis supported the association of nutrition with sarcopenia. CONCLUSIONS Herein, the characterization of a nutritional and metabolic signature of sarcopenia provides a firm basis and potential identification of specific targets and directions for the nutritional approach to the prevention and treatment of sarcopenia in aging populations.

Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.

Abstract: Human gene regulatory networks (GRN) can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs). Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data) accompanying this manuscript.

Interactome networks and human disease

Abstract: Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.

The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications.

Abstract: Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology Several types of immunotherapy, including adoptive cell transfer (ACT) and immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, and only subsets of cancer patients can benefit from them Immune infiltrates in the tumor microenvironment (TME) have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion, thus providing opportunities for the development of novel therapeutic strategies However, the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells With recent advances in single-cell technologies such as single-cell RNA sequencing (scRNA-seq) and mass cytometry, systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells In this review, we outline the recent progress in cancer immunotherapy, particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells, and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy We believe such a review could strengthen our understanding of the progress in cancer immunotherapy, facilitate the elucidation of immune cell modulation in tumor progression, and thus guide the development of novel immunotherapies for cancer treatment

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.