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Aging Epigenetics
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Vasily V. Ashapkin, Lyudmila I. Kutueva, Boris F. Vanyushin
In a transcriptome-wide investigation of aging-dependent gene expression in mice organs (liver, kidney, spleen, lung, and brain), mainly organ-specific differentially expressed genes (DEGs) were found: 6973 in the liver, 2325 in the kidney, 925 in the spleen, 1025 in the lung, and 15 in the brain [6]. Most DEGs (88%) were exclusively found in one organ. The number of overlapping DEGs rapidly decreased when more tissues were compared at the same time. Only one gene was found to be differentially expressed in all organs tested, namely Lilrb4. It encodes an immunoglobulin-like receptor that is involved in regulation of immune tolerance. Expression of Lilrb4 has been found to increase with aging. Five of the 11 other DEGs that are found in at least four organs are immunoglobulin lambda and kappa complex related, and all these DEGs showed increased gene expression during aging. Many functionally related gene sets altered their expression with aging in each organ, most of them exclusively in one organ. In all organs, except the liver, many gene sets involved in immunological processes were changed during aging. Generally, each organ seems to have a specific aging course.
LILRB4 promotes tumor metastasis by regulating MDSCs and inhibiting miR-1 family miRNAs
Published in OncoImmunology, 2022
Mei-Tzu Su, Sakiko Kumata, Shota Endo, Yoshinori Okada, Toshiyuki Takai
Polarization and reprogramming of MDSCs, which are able to be polarized from an M1 phenotype to an M2 phenotype or vice versa, affect tumor progression.7 Predominantly, tumor-associated MDSCs exhibit M2-like phenotype with pro-tumor activities. M2 phenotype MDSCs activate Treg to suppress Teff, whereas M1 counterparts have the opposing actions. Herein, we showed that the MDSCs from gp49B−/− tumor-bearing mice inhibit Treg activation and activate CD4 Teff proliferation, suggesting that LILRB4 could regulate the polarization of tumor-associated MDSCs. Several studies have shown that STAT3 activation results in the polarization of M2-TAM, and also results in the production of factors that promote tumor invasiveness, such as VEGFA and MMPs.44,45 Therefore, we propose that LILRB4 signaling may activate STAT3 to promote M2-polarization and induce the expression of VEGFA and MMP-9. In addition to expression on tumor-infiltrating immune cells, LILRB4 expression is also increased on human non-small cell lung cancer (NSCLC) cells, and LILRB4 overexpression enhances the migration and invasion of NSCLC cells by activating the ERK1/2-EMT/VEGFA axis.46 These results suggest that LILRB4 is involved in tumorigenesis by regulating gene expression associated with migration, invasion, and angiogenesis.
Identification of key biomolecules in rheumatoid arthritis through the reconstruction of comprehensive disease-specific biological networks
Published in Autoimmunity, 2020
The over-representation analyses based on situated DEGs for each tissue indicated significant results for generally immune systems related pathways: cytokine, chemokine, antigen processing and infection-related pathways (Figure 2). According to analyses results, immune systems pathway, infection associated pathways such as Staphylococcus aureus infection, Leishmaniasis, viral myocarditis and RA pathways as expected were enriched in synovial tissues (Figure 2(A)). On the other hand, in macrophages, similar results were obtained, however, cancer-associated pathways such as pathway in cancer, transcriptional misregulation in cancer, crucial signalling pathway such as MAPK signalling and cell structure related pathways, focal adhesion, extracellular matrix organization, were identified as enriched pathways (Figure 2(B)). The 25 DEGs common among all datasets were statistically enriched with interferon-gamma signalling, antigen presentation related pathway, pancreatic cancer and cytokine signalling pathways (Figure 2(C)). The top 15 significantly enriched pathways were represented in Figure 2, the rest of the results in (Supplementary Table 1). Accordingly, most of the proteins encoded by 25 core DEGs were mainly classified into six groups according to their functions: (i) SLC16A3, AQP9 and SLC39A8 act as transporter (ii) SERPINA1, GBP1, RAC2 and LILRB4 are enzyme modulator, (iii) S100A8, SPRY2, CXCL9 and LILRB4 serve as signalling molecule, (iv) HLA-DQB1 and LILRB4 are immunity proteins, (v) STAT1 and SPRY2 are TFs and (vi) KYNU and SPP1 are hydrolase (Figure 2(D)). Most of the classified genes (57%) are associated with immune system-related functions according to GeneCards descriptions (Table 2).
Immune checkpoint-based therapy in myeloid malignancies: a promise yet to be fulfilled
Published in Expert Review of Anticancer Therapy, 2019
Jan Philipp Bewersdorf, Maximilian Stahl, Amer M. Zeidan
LILRB4 is an immunoreceptor tyrosine-based inhibition motif-containing receptor that inhibits T-cell activity and has been shown to be associated with immune evasion of monocytic leukemia cells in both mouse models and human cells [38]. Importantly, antibody-mediated inhibition has been shown to inhibit AML development and makes LILRB4 another potential therapeutic target especially in monocytic AML [38,101].