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Topic Review
Functional T-Cell Changes with Aging, CMV Influence
Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. Researchers have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Researchers expand their results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, researchers studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). 
  • 244
  • 20 Dec 2023
Topic Review
The Link between SARS-CoV-2 Infection and Renal Cancer
Cancer has been described as a risk factor for greater susceptibility to SARS-CoV-2 infection and severe COVID-19, mainly for patients with metastatic disease. Conversely, to that reported for most solid and hematological malignancies, the few available clinical studies reported that the infection did not increase the risk of death in renal cancer patients. The expression on proximal tubular renal cells of the key players in cellular viral uptake, ACE2, TMPRSS2, and NRP1, seems to be the mechanism for the direct kidney injury seen in patients with COVID-19. Data from The Cancer Genome Atlas and experimental analyses on various renal cancer cell lines demonstrated that the above-reported receptors/cofactors are maintained by renal cancer cells. However, whether SARS-CoV-2 infection directly kills renal cancer cells or generates enhanced immunogenicity is a question worth investigating.
  • 244
  • 08 Jan 2024
Topic Review
Roles of Myeloid-Derived Suppressor Cells in Liver Disease
Liver disease-related mortality is a major cause of death worldwide. Hepatic innate and adaptive immune cells play diverse roles in liver homeostasis and disease. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells. MDSCs can be broadly divided into monocytic MDSCs and polymorphonuclear or granulocytic MDSCs, and they functionally interact with both liver parenchymal and nonparenchymal cells, such as hepatocytes and regulatory T cells, to impact liver disease progression. The infiltration and activation of MDSCs in liver disease can be regulated by inflammatory chemokines and cytokines, tumor-associated fibroblasts, epigenetic regulation factors, and gut microbiota during liver injury and cancer.
  • 244
  • 31 Jan 2024
Topic Review
Inflammasome Structures and Mechanisms of Action
Inflammasome complexes and their integral receptor proteins have essential roles in regulating the innate immune response and inflammation at the post-translational level. Yet despite their protective role, aberrant activation of inflammasome proteins and gain of function mutations in inflammasome component genes seem to contribute to the development and progression of human autoimmune and autoinflammatory diseases. 
  • 242
  • 20 Jul 2023
Topic Review
Story of Kinases and Adaptors Regulating TCR signaling
Tyrosine phosphorylation constitutes an essential mechanism of signal transduction in eukaryotic cells. In the immune system, this process is widely represented, and in T cells, the first biochemical event that occurs after antigenic recognition seems to be the phosphorylation of the tyrosine residues included in the CD3 chains. For T cells to develop, differentiate and proliferate, proper intracellular signaling is required, and the negative regulation of such signaling pathways is crucial to prevent autoimmune diseases or severe immunodeficiencies. Although not understood in depth, it is becoming increasingly clear that multiple negative regulatory loops exist along the TCR-signaling cascade. The tyrosine kinases Lck and ZAP70, together with the transmembrane adaptor LAT, are essential players in the transduction of TCR early signals, and the elimination of any of them causes serious alterations in the TCR-signaling cascade.
  • 240
  • 14 Sep 2023
Topic Review
L-Arginine Metabolism in Cancer
L-Arginine plays a crucial role in detoxification of ammonia—a protein breakdown product acts as a secretagogue and serves as a substrate for the synthesis of NO, an important signaling molecule that regulates vascular tone and cytotoxic functions of macrophages. L-Arg is also a precursor in the synthesis of L-ornithine and agmatine, creatine and polyamines. Metabolism of L-Arg is involved in immune cell regulation. It is now clear that L-Arg metabolism is engaged in the pathogenesis of tumor growth, inflammation, infectious diseases, and fibrotic processes, as well as physiological immunodeficiencies in newborns and pregnant women. 
  • 240
  • 21 Sep 2023
Topic Review
Breg-Mediated Immunoregulation in the Skin
Wound healing is a complex process involving a coordinated series of events aimed at restoring tissue integrity and function. Regulatory B cells (Bregs) are a subset of B lymphocytes that play an essential role in fine-tuning immune responses and maintaining immune homeostasis. Studies have suggested that Bregs are important players in cutaneous immunity. 
  • 240
  • 16 Jan 2024
Topic Review
Microbiota–Immunity–Hormone Interactions on Autoimmune Diseases and Infection
The immune system has to develop to defend against pathogens while simultaneously tolerating the beneficial microorganisms that coexist symbiotically with the host. Moreover, the microbiota in the large intestine plays a significant role in preserving mucosal and systemic homeostasis. The interaction between the large intestine microbiota and local immune cells is crucial for directing specific immune responses and, consequently, for performing immunomodulatory functions.
  • 240
  • 21 Mar 2024
Topic Review
Dendritic Cell-Based Vaccine Efficacy through Genetic Modulation
The dendritic cell (DC) vaccine anti-cancer strategy involves tumour-associated antigen loading and maturation of autologous ex vivo cultured DCs, followed by infusion into the cancer patient. This strategy stemmed from the idea that to induce a robust anti-tumour immune response, it was necessary to bypass the fundamental immunosuppressive mechanisms of the tumour microenvironment that dampen down endogenous innate immune cell activation and enable tumours to evade immune attack. Even though the feasibility and safety of DC vaccines have long been confirmed, clinical response rates remain disappointing. Hence, the full potential of DC vaccines has yet to be reached. Whether this cellular-based vaccination approach will fully realise its position in the immunotherapy arsenal is yet to be determined. Attempts to increase DC vaccine immunogenicity will depend on increasing people's understanding of DC biology and the signalling pathways involved in antigen uptake, maturation, migration, and T lymphocyte priming to identify amenable molecular targets to improve DC vaccine performance.
  • 237
  • 28 Nov 2023
Topic Review
Immunosenescence and Cytomegalovirus
Aging induces numerous physiological alterations, with immunosenescence emerging as a pivotal factor. This phenomenon has attracted both researchers and clinicians, prompting profound questions about its implications for health and disease. Among the contributing factors, one intriguing actor in this complex interplay is human cytomegalovirus (CMV), a member of the herpesvirus family. Latent CMV infection exerts a profound influence on the aging immune system, potentially contributing to age-related diseases.
  • 236
  • 22 Jan 2024
Topic Review
ATF4 Role during HIV-1 Replication
Activating transcription factor 4 (ATF4) is a transcription factor known to regulate genes associated with the sensing of cellular stress such as amino acid deprival, protein misfolding, growth arrest, and cell death. Despite its key role at the crossroads of immune and stress responses, the precise impact of ATF4 during viral infections remains unclear. Thus, ATF4 has a dual role in promoting cell survival or cell death, but also in limiting infection or participating in viral replication.
  • 235
  • 18 Mar 2024
Topic Review
Long COVID in Older Adults
As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating.
  • 234
  • 14 Nov 2023
Topic Review
NOD Contibutes to the Immune and Metabolic Health
Nucleotide-binding oligomerization domain-like (NOD) receptors rely on the interface between immunity and metabolism. Dietary factors constitute critical players in the activation of innate immunity and modulation of the gut microbiota.
  • 231
  • 20 Feb 2024
Topic Review
Targeted Cytokines as Cancer Therapeutics in Glioblastoma
Cytokines are secreted proteins that engage the extracellular domains of cell surface receptors and regulate immune response and homeostasis. Cytokines can be classified based on their roles as pro- or anti-inflammatory cytokines or on cellular origin.
  • 227
  • 15 Sep 2023
Topic Review
HIV Lifecycle
The theory of immune regulation involves a homeostatic balance between T-helper 1 (Th1) and T-helper 2 (Th2) responses. The Th1 and Th2 theories were introduced in 1986 as a result of studies in mice, whereby T-helper cell subsets were found to direct different immune response pathways. Subsequently, this hypothesis was extended to human immunity, with Th1 cells mediating cellular immunity to fight intracellular pathogens, while Th2 cells mediated humoral immunity to fight extracellular pathogens. Several disease conditions were later found to tilt the balance between Th1 and Th2 immune response pathways, including HIV infection, but the exact mechanism for the shift from Th1 to Th2 cells was poorly understood. 
  • 225
  • 22 Jan 2024
Topic Review
miRNAs Released by Osteoclasts
Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation, pain, and ultimately, bone erosion of the joints. The causes of this disease are multifactorial, including genetic factors, such as the presence of the human leukocyte antigen (HLA)-DRB1*04 variant, alterations in the microbiota, or immune factors including increased cytotoxic T lymphocytes (CTLs), neutrophils, or elevated M1 macrophages which, taken together, produce high levels of pro-inflammatory cytokines. The function exerted by osteoclasts on osteoblasts and other osteoclasts by means of the release of exosomal microRNAs (miRNAs) was focused on. Based on a thorough revision, researchers classified these molecules into three categories according to their function: osteoclast inhibitors (miR-23a, miR-29b, and miR-214), osteoblast inhibitors (miR-22-3p, miR-26a, miR-27a, miR-29a, miR-125b, and miR-146a), and osteoblast enhancers (miR-20a, miR-34a, miR-96, miR-106a, miR-142, miR-199a, miR-324, and miR-486b). 
  • 225
  • 20 Feb 2024
Topic Review
Role of Extracellular Vesicles in SARS-CoV-2 Infection
Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, and entry control characteristics similar to viral infections. Viruses, on the other hand, depend on host metabolic machineries to fulfill their biosynthetic requirements. Due to potential advantages such as biocompatibility, biodegradation, and efficient immune activation, EVs have emerged as potential therapeutic targets against the SARS-CoV-2 infection. 
  • 222
  • 16 Jan 2024
Topic Review
Immune Checkpoints in Solid Organ Transplantation
The immune system spontaneously recognizes and destroys foreign cells and organs when grafted into a genetically different individual. Organ transplantation is only successful because of the use of life-long immunosuppressive medications, which comes at the cost of severe toxicities. Thus, a major breakthrough in transplantation would be to be able to educate the immune system to accept grafted organs in the long term. A possible way to do that would be to exploit a physiological retro-control of the immune cells, which is based on the timely and coordinated expression of cell-surface receptors with inhibitory activities. In cancer, blocking these receptors (or Immune Checkpoints) boosts the anti-tumor functions of certain immune cells (the T-lymphocytes), with highly significant clinical benefits. Thus, it is likely that opposite actions, such as increasing the expression or the function of these receptors, would result in the dampening of the immune response against foreign organs.
  • 213
  • 22 Jan 2024
Topic Review
Th2 Pathways in Gastric Metaplasia
Gastric cancer is one of the leading causes of cancer deaths worldwide, with chronic gastritis representing the main predisposing factor initiating the cascade of events leading to metaplasia and eventually progressing to cancer. Th2 immune responses play a major role in the events causing chronic inflammation leading to tumorigenesis.
  • 213
  • 07 Feb 2024
Topic Review
Diverse Immune Cells in Behçet’s Disease
Behçet’s disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD’s pathogenesis, focusing on established genetic factors. Studies reveal that HLA-B*51 is the primary genetic risk factor, but non-HLA genes (ERAP1, IL-10, IL23R/IL-12RB2), as well as innate immunity genes (FUT2, MICA, TLRs), also contribute. Genome-wide studies emphasize the significance of ERAP1 and HLA-I epistasis. These variants influence antigen presentation, enzymatic activity, and HLA-I peptidomes, potentially leading to distinct autoimmune responses. 
  • 211
  • 27 Nov 2023
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