Leukocyte immunoglobulin (Ig)-like receptors (LILRs) on human chromosome 19q13.4 encode 11 immunoglobulin superfamily receptors, exhibiting genetic diversity within and between human populations. Among the LILR genes, the genomic region surrounding LILRB3 and LILRA6 has yet to be fully characterized due to their significant sequence homology, which makes it difficult to differentiate between them. To examine the LILRB3 and LILRA6 genomic region, a tool named JoGo-LILR CN Caller, which can call copy number from short-read whole genome sequencing (srWGS) data, was applied to an extensive international srWGS dataset comprising 2,504 samples. During this process, a previously unreported loss of both LILRB3 and LILRA6 was detected in three samples. Using long-read sequencing of these samples, we have discovered a novel large deletion (33,692 bp) in the LILRB3 and LILRA6 genomic regions in the Japanese population. This deletion spanned three genes, LILRB3, LILRA6, and LILRB5, resulting in LILRB3 exons 12-13 being located immediately downstream of LILRB5 exons 1-12 with the loss of LILRA6, suggesting the potential expression of a hybrid gene between LILRB5 and LILRB3 (LILRB5-3). Transcription and subsequent translation of the LILRB5-3 hybrid gene were also verified. The hybrid junction was located within the intracellular domain, resulting in an LILRB5 extracellular domain fused to a partial LILRB3 intracellular domain with three immunoreceptor tyrosine-based inhibitory motifs (ITIMs), suggesting that LILRB5-3 acquired a novel signaling function. Further application of the JoGo-LILR tool to srWGS samples suggested the presence of the LILRB5-3 hybrid gene in the CEU population. Our findings provide insight into the genetic and functional diversity of the LILR family.

This study aims to harness bioinformatics to identify prognostic immune-related genes in clear cell renal cell carcinoma (ccRCC), focusing particularly on LILRB3. It evaluates LILRB3\'s expression in ccRCC, its association with patient prognosis, and its potential as a biomarker for predicting survival, thereby providing a preliminary basis for the diagnosis of ccRCC. Utilizing The Cancer Genome Atlas (TCGA) datasets and an immune gene set, we sought immune-related genes with elevated expression in ccRCC. Seventy-two normal tissue samples and 531 ccRCC samples were analyzed, and differential genes were identified with a screening criterion of fold change (FC) > 2 and P value < 0.01. Survival analysis and receiver operating characteristic (ROC) curve analysis were employed to discover genes of prognostic and diagnostic relevance to ccRCC. Pearson correlation analysis with a cutoff of |r|≥ 0.5, facilitated by cBioPortal, assessed genes co-expressed with LILRB3. The DAVID online tool conducted functional and pathway enrichment analyses for LILRB3-coexpressed genes. The TIMER and TCIA databases were utilized to explore LILRB3\'s influence on immune infiltration in the tumor microenvironment and its relation to key immunological checkpoints. Screening the TCGA database revealed 3719 up-regulated differential genes in ccRCC, with 355 overlapping immune-related genes. Survival analysis of these 355 genes revealed 100 with significant survival impact. ROC curve analysis pinpointed the top 10 genes, including LILRB3, with the highest diagnostic efficiency. LILRB3 emerged as an independent risk factor from the Cox risk regression model. GO and KEGG analyses linked LILRB3 to various biological processes, including chemokine signaling pathways, immunological response, antigen processing and presentation, inflammatory response, T cell co-stimulation, and signal transduction. LILRB3 significantly affected ccRCC immune infiltration and correlated positively with several immunological checkpoints, such as PD-1, LAG3, IDO1, PD-L1, CTLA4, TIM3, TIGIT, and VISTA. LILRB3 shows higher expression levels in ccRCC than in normal tissues and correlates with poor patient prognosis. Its impactful role in the immune infiltration of the RCC microenvironment suggests that LILRB3 could serve as a novel target for ccRCC treatment and prognosis, underlining its diagnostic and prognostic significance.

LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment.
Potential miRNAs binding to the 3\'-untranslated region (3\'-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo.
LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth.
MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.

BACKGROUND: Gene expression profiles have important significance for gene expression characteristics and further functional studies. More attention has been given to the expression databases in humans and mice, but less attention has been given to rats, while rat models also play an irreplaceable role in biomedical experiments.
RESULTS: To depict the rat gene expression profiles in mRNA expression levels, we analyzed over 2,700 RNA sequencing (RNA-Seq) samples from 48 tissues, 40 primary cell types and 25 cell lines; and then mapped them to the latest version of the rat genome reference, mRatBN7.2. Based on these datasets and reanalysis, we constructed a new database, the Omic Horizon Expression Database ( http://immudb.bjmu.edu.cn/expression.html ), which allows expressional profile query of over 25,000 rat genes based on non-redundant gene symbols. The database supports requests using gene symbols (or alias), Ensemble and Entrez gene IDs. Gene expression profiles can be queried in three categories: tissues, primary cells and cell lines. Application examples including expression profiling and comparison, as well as identification of novel rat genes, were illustrated to show the utility of the database.
CONCLUSIONS: As an omic resource, the Omic Horizon Expression Database provides horizons of gene expression profiles across various tissues and cells, which greatly facilitates the identification of rat genes as well as functional clues.

Neutrophils have a crucial role in defense against microbes. Immune receptors allow neutrophils to sense their environment, with many receptors functioning to recognize signs of infection and to promote antimicrobial effector functions. However, the neutrophil response must be tightly regulated to prevent excessive inflammation and tissue damage, and regulation is achieved by expression of inhibitory receptors that can raise activation thresholds. The leukocyte immunoglobulin-like receptor (LILR) family contain activating and inhibitory members that can up- or down-regulate immune cell activity. New ligands and functions for LILR continue to emerge. Understanding the role of LILR in neutrophil biology is of general interest as they can activate and suppress antimicrobial responses of neutrophils and because several human pathogens exploit these receptors for immune evasion. This review focuses on the role of LILR in neutrophil biology. We focus on the current knowledge of LILR expression on neutrophils, the known functions of LILR on neutrophils, and how these receptors may contribute to shaping neutrophil responses during infection.

OBJECTIVE: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines.
METHODS: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay.
RESULTS: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and β2-microglobulin and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines.
CONCLUSIONS: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, β2-microglobulin, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.