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Seminars in Cancer Biology Aug 2020Cancer and autoimmune disease are closely related, and many therapeutic antibodies are widely used in clinics for the treatment of both diseases. Among them, the... (Review)
Review
Cancer and autoimmune disease are closely related, and many therapeutic antibodies are widely used in clinics for the treatment of both diseases. Among them, the anti-CD20 antibody has proven to be effective against both lymphoid malignancy and autoimmune disease. Moreover, immune checkpoint blockade using the anti-PD1/PD-L1/CTLA4 antibody has improved the prognosis of patients with refractory solid tumors. At the same time, however, over-enhancement of immunoreaction can induce autoimmune reaction. Although anti-TNF antibody therapies represent a breakthrough in the treatment of autoimmune diseases, optimal management is required to control the serious associated issues, including development and progression of cancer, and it is becoming more and more important to control the immunoreaction. In addition, next-generation antibody therapeutics such as antibody-drug conjugates and bispecific antibodies, are anticipated to treat uncontrolled cancer and autoimmune disease. IL-7R signaling plays an important role in the development and progression of both lymphoid malignancy and autoimmune disease. In addition, abnormal homing activity and steroid resistance caused by IL-7R signaling may worsen prognosis. Therefore, anti-IL-7R targeting antibody therapies that enable suppression of such pathophysiological status have the potential to be beneficial for the treatment of both diseases. In this review, we discuss current antibody therapeutics in cancer and autoimmune disease, and describe a new therapeutic strategy for immunoregulation including IL-7R targeting antibodies.
Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Autoimmune Diseases; Humans; Immunotherapy; Neoplasms; Receptors, Interleukin-7
PubMed: 31181267
DOI: 10.1016/j.semcancer.2019.06.001 -
F1000Research 2018Helminth parasites are complex metazoans that belong to different taxonomic families but that collectively share the capacity to downregulate the host immune response... (Review)
Review
Helminth parasites are complex metazoans that belong to different taxonomic families but that collectively share the capacity to downregulate the host immune response directed toward themselves (parasite-specific immunoregulation). During long-standing chronic infection, these helminths appear able to suppress immune responses to bystander pathogens/antigens and atopic, autoimmune, and metabolic disorders. Helminth-induced immunoregulation occurs through the induction of regulatory T cells or Th2-type cells (or both). However, secreted or excreted parasite metabolites, proteins, or extracellular vesicles (or a combination of these) may also directly induce signaling pathways in host cells. Therefore, the focus of this review will be to highlight recent advances in understanding the immune responses to helminth infection, emphasizing the strategies/molecules and some of the mechanisms used by helminth parasites to modulate the immune response of their hosts.
Topics: Animals; Helminthiasis; Helminths; Host-Parasite Interactions; Humans; Intestinal Diseases, Parasitic; T-Lymphocytes, Regulatory; Th2 Cells
PubMed: 30416709
DOI: 10.12688/f1000research.15596.1 -
Acta Biomaterialia Jan 2023Wound repair involves a sophisticated process that includes angiogenesis, immunoregulation and collagen deposition. However, weak revascularization performance and the...
Wound repair involves a sophisticated process that includes angiogenesis, immunoregulation and collagen deposition. However, weak revascularization performance and the lack of biochemical cues to trigger immunomodulatory function currently limit biomaterial applications for skin regeneration and tissue engineering. Herein, we fabricate a new bioactive polypeptide hydrogel (QK-SF) constituted by silk fibroin (SF) and a vascular endothelial growth factor mimetic peptide KLTWQELYQLKYKGI (QK) for tissue regeneration by simultaneously promoting vascularization and macrophage polarization. Our results showed that this QK-SF hydrogel can be prepared via an easy manufacturing process, and exhibited good gel stability and low cytotoxicity to cultured human umbilical vein endothelial cells (HUVECs) via both live/dead and cell counting kit-8 assays. Importantly, this QK-SF hydrogel triggered macrophage polarization from M1 into M2, as exemplified by the enhanced expression of the M2 marker and decreased expression of the M1 marker in RAW264.7 cells. Furthermore, the QK-SF hydrogel showed high capacity for inducing endothelial growth, migration and angiogenesis, which were proved by increased expression of angiogenesis-related genes in HUVECs. Consistent with in vitro findings, in vivo data show that the QK-SF hydrogel promoted M2 polarization, keratinocyte differentiation, and collagen deposition in the mouse skin wound model in immunohistochemistry assay. Furthermore, this QK-SF hydrogel can reduce inflammation, induce angiogenesis and promote wound healing as exemplified by the increased vessel formation and decreased wound area in the mouse skin wound model. Altogether, these results indicate that the bioactive QK-SF hydrogel plays dual functional roles in promoting angiogenesis and immunoregulation for tissue regeneration. STATEMENT OF SIGNIFICANCE: The QK-SF hydrogel plays dual functional roles in promoting angiogenesis and immunoregulation for tissue repair and wound healing. The QK-SF hydrogel can be prepared via an easy manufacturing process, and exhibited good gel stability and low cytotoxicity to cultured HUVECs. The QK-SF hydrogel triggered macrophage polarization from M1 into M2. The QK-SF hydrogel showed high capacity for inducing endothelial growth, migration and angiogenesis. The QK-SF hydrogel promoted M2 polarization, keratinocyte differentiation, and collagen deposition.
Topics: Mice; Animals; Humans; Hydrogels; Vascular Endothelial Growth Factor A; Wound Healing; Collagen; Human Umbilical Vein Endothelial Cells; Macrophages
PubMed: 36396041
DOI: 10.1016/j.actbio.2022.11.002 -
Cell & Bioscience May 2023Nicotinamide adenine dinucleotide (NAD) is a critical metabolite that acts as a cofactor in energy metabolism, and serves as a cosubstrate for non-redox NAD-dependent... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is a critical metabolite that acts as a cofactor in energy metabolism, and serves as a cosubstrate for non-redox NAD-dependent enzymes, including sirtuins, CD38 and poly(ADP-ribose) polymerases. NAD metabolism can regulate functionality attributes of innate and adaptive immune cells and contribute to inflammatory responses. Thus, the manipulation of NAD bioavailability can reshape the courses of immunological diseases. Here, we review the basics of NAD biochemistry and its roles in the immune response, and discuss current challenges and the future translational potential of NAD research in the development of therapeutics for inflammatory diseases, such as COVID-19.
PubMed: 37165408
DOI: 10.1186/s13578-023-01031-5 -
Molecules (Basel, Switzerland) May 2023L-theanine (N-ethyl-γ-glutamine) is the main amino acid in tea leaves. It not only contributes to tea flavor but also possesses several health benefits. Compared with... (Review)
Review
L-theanine (N-ethyl-γ-glutamine) is the main amino acid in tea leaves. It not only contributes to tea flavor but also possesses several health benefits. Compared with its sedative and calming activities, the immunomodulatory effects of L-theanine have received less attention. Clinical and epidemiological studies have shown that L-theanine reduces immunosuppression caused by strenuous exercise and prevents colds and influenza by improving immunity. Numerous cell and animal studies have proven that theanine plays an immunoregulatory role in inflammation, nerve damage, the intestinal tract, and tumors by regulating γδT lymphocyte function, glutathione (GSH) synthesis, and the secretion of cytokines and neurotransmitters. In addition, theanine can be used as an immunomodulator in animal production. This article reviews the research progress of L-theanine on immunoregulation and related mechanisms, as well as its application in poultry and animal husbandry. It is hoped that this work will be beneficial to future related research.
Topics: Animals; Glutamates; Cytokines; Immunity; Tea
PubMed: 37175254
DOI: 10.3390/molecules28093846 -
Cancer Cell International Jun 2023C-type lectin domain family 1 member B (CLEC1B, encoding the CLEC-2 protein), a member of the C-type lectin superfamily, is a type II transmembrane receptor involved in...
BACKGROUND
C-type lectin domain family 1 member B (CLEC1B, encoding the CLEC-2 protein), a member of the C-type lectin superfamily, is a type II transmembrane receptor involved in platelet activation, angiogenesis, and immune and inflammatory responses. However, data regarding its function and clinical prognostic value in hepatocellular carcinoma (HCC) remain scarce.
METHODS
The expression of CLEC1B was explored using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RT-qPCR, western blot, and immunohistochemistry assays were employed to validate the downregulation of CLEC1B. Univariate Cox regression and survival analyses were used to evaluate the prognostic value of CLEC1B. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential association between cancer hallmarks and CLEC1B expression. The TISIDB database was applied to search for the correlation between immune cell infiltration levels and CLEC1B expression. The association between CLEC1B and immunomodulators was conducted by Spearman correlation analysis based on the Sangerbox platform. Annexin V-FITC/PI apoptosis kit was used for the detection of cell apoptosis.
RESULTS
The expression of CLEC1B was low in various tumors and exhibited a promising clinical prognostic value for HCC patients. The expression level of CLEC1B was tightly associated with the infiltration of various immune cells in the HCC tumor microenvironment (TME) and positively correlated with a bulk of immunomodulators. In addition, CLEC1B and its related genes or interacting proteins are implicated in multiple immune-related processes and signaling pathways. Moreover, overexpression of CLEC1B significantly influenced the treatment effects of sorafenib on HCC cells.
CONCLUSIONS
Our results reveal that CLEC1B could serve as a potential prognostic biomarker and may be a novel immunoregulator for HCC. However, its function in immune regulation should be further explored.
PubMed: 37308868
DOI: 10.1186/s12935-023-02939-1 -
Frontiers in Immunology 2023Ras guanine nucleotide-releasing protein 2 (RASGRP2), one of the guanine nucleotide exchange factors (GEFs), has attracted much attention in recent years. However, the...
BACKGROUND
Ras guanine nucleotide-releasing protein 2 (RASGRP2), one of the guanine nucleotide exchange factors (GEFs), has attracted much attention in recent years. However, the correlation between RASGRP2 and immune infiltration and malignant features in lung adenocarcinoma (LUAD) has rarely been mentioned.
METHODS
The Limma package and the LASSO regression model were performed to screen for differentially expressed genes. Data from the TCGA and 5 GEO databases were used to explore the expression level of RASGRP2 in LUAD patients. A weighted co-expression network and LinkFinder module were established to find the related genes of RASGRP2. The ESTIMATE algorithm was used to analyze the correlation between RASGRP2 and immune infiltration in LUAD. Tumor-infiltrating immune cells were sorted and sequenced at the single-cell level to analyze differences in RASGRP2. Real-time PCR and immunohistochemistry were performed in the real-world cohort to verify the expression of RASGRP2 and its correlation with immune-related genes. Clone formation and EdU assays were used to verify the proliferation ability. The proportion of apoptotic cells was analyzed by flow cytometry. Observation of mitochondrial membrane potential (MMP) changes by fluorescence microscopy.
RESULTS
Our results suggested that decreased RASGRP2 was associated with worse clinical parameters and prognosis in LUAD patients. And we constructed a FLI1-HSA-miR-1976-RASGRP2 transcriptional network to support the role of RASGRP2. Enrichment analysis revealed that RASGRP2 was involved in lymphocyte activation and leukocyte adhesion. RASGRP2 was found to be positively correlated with the infiltration of most immune cells, immunoregulators, and chemokines in a subsequent study. Meanwhile, the real-world cohort confirmed that the expression levels of PDCD1, CTLA4, CD40LG, CCL14, CXCR5, and CCR7 were higher in the high-RASGRP2 expression group. Cytological experiments proved that RASGRP2 inhibited cell proliferation in LUAD by regulating mitochondrial-dependent apoptosis.
CONCLUSION
RASGRP2 was a potential immune-related biomarker of LUAD. In addition, RASGRP2 was involved in the malignant progression of LUAD through the regulation of mitochondrial-dependent apoptosis.
Topics: Humans; Mitochondria; Apoptosis; Adenocarcinoma of Lung; Algorithms; Lung Neoplasms; Guanine Nucleotide Exchange Factors
PubMed: 36817422
DOI: 10.3389/fimmu.2023.1100231 -
Frontiers in Oncology 2022As a transcriptional factor and the negative regulator of alpha fetal protein (AFP), Zinc fingers and homeoboxes 2 (ZHX2) has a well-established role in protection... (Review)
Review
As a transcriptional factor and the negative regulator of alpha fetal protein (AFP), Zinc fingers and homeoboxes 2 (ZHX2) has a well-established role in protection against hepatocellular carcinoma (HCC). However, recent studies have suggested ZHX2 as an oncogene in clear cell renal cell carcinoma (ccRCC) and triple-negative breast cancer (TNBC). Moreover, mounting evidence has illustrated a much broader role of ZHX2 in multiple cellular processes, including cell proliferation, cell differentiation, lipid metabolism, and immunoregulation. This comprehensive review emphasizes the role of ZHX2 in health and diseases which have been more recently uncovered.
PubMed: 36465389
DOI: 10.3389/fonc.2022.1038890 -
Cellular & Molecular Immunology Aug 2006Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate... (Review)
Review
Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.
Topics: Cell Adhesion Molecules; Dendritic Cells; Humans; Immunity; Lectins, C-Type; Receptors, Cell Surface; Receptors, Pattern Recognition; Tumor Escape
PubMed: 16978536
DOI: No ID Found -
Aging and Disease Apr 2020Gut microbiome refers to the microbes that live in human digestive tract and are symbiotic with the human body. They participate in the regulation of various... (Review)
Review
Gut microbiome refers to the microbes that live in human digestive tract and are symbiotic with the human body. They participate in the regulation of various physiological and pathological processes of the human body and are associated with various diseases. The pathological process of osteoporosis is affected by gut microbes. The molecular mechanisms of osteoporosis mainly include: 1) Intestinal barrier and nutrient absorption (involving SCFAs). 2) Immunoregulation (Th-17 and T-reg cells balance). 3) Regulation of intestinal-brain axis (involving 5-HT). Gut microbes can increase bone mass and improve osteoporosis by inhibiting osteoclast proliferation and differentiation, inducing apoptosis, reducing bone resorption, or promoting osteoblast proliferation and maturation. However, the therapeutic effect of gut microbes on osteoporosis remains to be further proven. At present, some of the findings on the impact of gut microbes on osteoporosis has been applied in clinical, including early diagnosis and intervention of osteoporosis and adjuvant therapy. In this article, we reviewed the molecular mechanisms underlying the regulatory effect of gut microbes on osteoporosis and the clinical practice of using gut microbes to improve bone health.
PubMed: 32257552
DOI: 10.14336/AD.2019.0523