Protective cellular immune responses have been difficult to study in fish, due to lack of basic understanding of their T cell populations, and tools to study them. Cellular immunity is thus mostly ignored in vaccination and infection studies compared to humoral responses. High throughput sequencing, as well as access to well assembled genomes, now advances studies of cellular responses. Here we have used such resources to describe organization of T cell receptor beta genes in Atlantic salmon. Salmonids experienced a unique whole genome duplication approximately 94 million years ago, which provided these species with many functional duplicate genes, where some duplicates have evolved new functions or sub-functions of the original gene copy. This is also the case for T cell receptor beta, where Atlantic salmon has retained two paralogue T cell receptor beta regions on chromosomes 01 and 09. Compared to catfish and zebrafish, the genomic organization in both regions is unique, each chromosomal region organized with dual variable- diversity- joining- constant genes in a head to head orientation. Sequence identity of the chromosomal constant sequences between TRB01 and TRB09 is suggestive of rapid diversification, with only 67 percent as opposed to the average 82-90 percent for other duplicated genes. Using virus challenged samples we find both regions expressing bona fide functional T cell receptor beta molecules. Adding the 292 variable T cell receptor alpha genes to the 100 variable TRB genes from 14 subgroups, Atlantic salmon has one of the most diverse T cell receptor alpha beta repertoire of any vertebrate studied so far. Perhaps salmonid cellular immunity is more advanced than we have imagined.
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http://dx.doi.org/10.3389/fimmu.2022.930312 | DOI Listing |
JCI Insight
January 2025
Department of Biomedical Engineering, Oregon Health and Science University, Portland, United States of America.
Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Laboratory Medicine, Division of Translational Cancer Researc, Lund University Cancer Centre, Lund University, Lund, Sweden.
The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.
View Article and Find Full Text PDFCurr Osteoporos Rep
January 2025
Department of Immunology, Tufts University, Boston, MA, 02111, USA.
Purpose Of Review: The purpose of this review is to summarize the current understanding of cell-autonomous innate immune pathways that contribute to bone homeostasis and disease.
Recent Findings: Germ-line encoded pattern recognition receptors (PRRs) are the first line of defense against danger and infections. In the bone microenvironment, PRRs and downstream signaling pathways, that mount immune defense, interface intimately with the core cellular processes in bone cells to alter bone formation and resorption.
Immunol Res
January 2025
Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Türkiye.
B-cell acute lymphoblastic leukemia (B-ALL) is the most common form of cancer diagnosed in children. While the majority of patients survive with conventional treatment, chemotherapeutic agents have adverse effects and the potential for relapse persists even after full recovery. Given their pivotal function in anti-cancer immunity, there has been a surge in research exploring the potential of natural killer (NK) cells in immunotherapy, which has emerged as a promising avenue for treating leukemia.
View Article and Find Full Text PDFImmunol Res
January 2025
Department of Otolaryngology, Qingdao Traditional Chinese Medicine Hospital (Qingdao Hiser Hospital), Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao, 266033, Shandong, People's Republic of China.
Baicalein, one of the major active flavonoids found in Scutellaria baicalensis, has been revealed to exhibit potent anti-inflammatory properties in allergic airway inflammation. This study aimed to explore the role of baicalein and its relevant mechanism in the treatment of allergic rhinitis (AR). The bioinformatics tools were used to predict the targets of baicalein and AR-related genes.
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