immune homeostasis

Regulatory T cells (Tregs) play a crucial role in the homeostasis of the immune response. Tregs are mainly generated in the thymus and are characterized by the expression of Foxp3, which is considered the Treg master transcription factor. In addition, Tregs can be induced from naïve CD4+ T cells to express Foxp3 under specific conditions both in vivo (pTregs) and in vitro (iTregs). Both subsets tTregs and pTregs are necessary for the establishment of immune tolerance to self and non-self antigens. Although it has been postulated that iTregs may be less stable compared to tTregs, mainly due to epigenetic differences, accumulating evidence in animal models shows that iTregs are stable in vivo and could be used for the treatment of inflammatory disorders including autoimmune diseases and allogeneic transplant rejection...

Peri-implantitis (PI) is a chronic, inflammatory, and infectious disease which affects dental implants and has certain similarities to periodontitis (PD). Evidence has shown that PD may be related to several types of systemic disorders, such as diabetes and insulin resistance, cardiovascular diseases, respiratory tract infections, adverse pregnancy outcomes, and neurological disorders. Furthermore, some types of bacteria in PD can also be found in PI, leading to certain similarities in the immunoinflammatory responses in the host...

When cells proliferate, stress on DNA replication or exposure to endogenous or external insults frequently results in DNA damage. DNA-Damage Response (DDR) networks are complex signaling pathways used by multicellular organisms to prevent DNA damage. Depending on the type of broken DNA, the various pathways, Base-Excision Repair (BER), Nucleotide Excision Repair (NER), Mismatch Repair (MMR), Homologous Recombination (HR), Non-Homologous End-Joining (NHEJ), Interstrand Crosslink (ICL) repair, and other direct repair pathways, can be activated separately or in combination to repair DNA damage...

Innate immune response is the first line of defense for the host against virus invasion. One important response is the synthesis and secretion of type I interferon (IFN-I) in the virus-infected host cells. Here, we found that respiratory syncytial virus (RSV) infection induced high expression of TRIM25, which belongs to the tripartite motif-containing (TRIM) family of proteins. TRIM25 bound and activated retinoic acid-inducible gene I (RIG-I) by K63-linked ubiquitination. Accordingly, RIG-I mediated the production of IFN-I mainly through the nuclear factor kappa-B (NF-κB) pathway in respiratory epithelial cells...

The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, genetic studies of the role of specific NFκB transcription factors in sleep have been limited. Drosophila fruit flies carry three genes encoding NFκB transcription factors, Dorsal, Dorsal Immunity Factor (Dif), and Relish. We previously found that loss of the Relish gene from fat body suppressed daily nighttime sleep, and abolished infection-induced sleep...

In recent years, much has been written about the possibilities of using exogenous sodium butyrate in the prevention and treatment of gastrointestinal diseases, in prehabilitation, in peri- and postoperative treatment, as well as its local application. It became possible thanks to the development of a special formulation (microencapsulation technique) enabling the delivery of unstable butyrate compounds to the large intestine, where it is used primarily as a source of energy. It also plays a key role in maintaining body homeostasis by maintaining the integrity of the intestinal epithelium and stimulating the intestinal immune system...

Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against "self". In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients' life, reduces the spectrum of the available therapeutic options...

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. The target molecules and signaling pathways, such as Wnt/β-catenin and OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential in the treatment of OP...

BACKGROUND: Accumulating evidence underscores the pivotal role of heightened inflammation in the pathophysiology of stress-related diseases, but the underlying mechanisms remain elusive. The complement system, a key effector of the innate immune system, produces the C5-cleaved activation product C5a upon activation, initiating inflammatory responses through the canonical C5a receptor 1 (C5aR1). While C5aR1 is expressed in stress-responsive brain regions, its role in stress responsiveness remains unknown...

In the context of aging, the susceptibility to infectious diseases increases, leading to heightened morbidity and mortality. This phenomenon, termed immunosenescence, is characterized by dysregulation in the aging immune system, including abnormal alterations in lymphocyte composition, elevated basal inflammation, and the accumulation of senescent T cells. Such changes contribute to increased autoimmune diseases, enhanced infection severity, and reduced responsiveness to vaccines. Utilizing aging animal models becomes imperative for a comprehensive understanding of immunosenescence, given the complexity of aging as a physiological process in living organisms...

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition...

ALK-positive NSCLC patients demonstrate initial responses to ALK tyrosine kinase inhibitor (TKI) treatments, but eventually develop resistance, causing rapid tumor relapse and poor survival rates. Growing evidence suggests that the combination of drug and immune therapies greatly improves patient survival; however, due to the low immunogenicity of the tumors, ALK-positive patients do not respond to currently available immunotherapies. Tumor-associated macrophages (TAMs) play a crucial role in facilitating lung cancer growth by suppressing tumoricidal immune activation and absorbing chemotherapeutics...

Ammonia-N, as the most toxic nitrogenous waste, has high toxicity to marine animals. However, the interplay between ammonia-induced neuroendocrine toxicity and intestinal immune homeostasis has been largely overlooked. Here, a significant concordance of metabolome and transcriptome-based "cholinergic synapse" supports that plasma metabolites acetylcholine (ACh) plays an important role during NH4 Cl exposure. After blocking the ACh signal transduction, the release of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the cerebral ganglia increased, while the release of NPF in the thoracic ganglia and NE in the abdominal ganglia, and crustacean hyperglycemic hormone (CHH) and neuropeptide F (NPF) in the eyestalk decreased, finally the intestinal immunity was enhanced...

Lymph nodes (LNs) are organs of the immune system, critical for maintenance of homeostasis and initiation of immune responses, yet there are few models that accurately recapitulate LN functions in vitro. To tackle this issue, an engineered murine LN (eLN) was developed, replicating key cellular components of the mouse LN; incorporating primary murine lymphocytes, fibroblastic reticular cells (FRCs), and lymphatic endothelial cells (LECs). T and B cells compartments are incorporated within the eLN that mimic LN cortex and paracortex architectures...

This issue highlights and details the programme and scientific presentations at the International Eosinophil Society's 12th biennial Symposium, which was held in Hamilton, Ontario, Canada in July 2023. The meeting included sessions on regulation of eosinophil development; cell death, stress, and autophagy in eosinophils; local immunity interactions of eosinophils with multiple cell types; eosinophils in host defense; eosinophils and mast cells in gastrointestinal disorders; reciprocal interactions between eosinophils and the microbiome in homeostasis and dysbiosis; and, eosinophils in tissue injury and repair, in tumor biology and cancer therapy...

More and more evidence shows that abnormal lipid metabolism leads to immune system dysfunction in AMD and promotes the occurrence of AMD by changing the homeostasis of ocular inflammation. However, the molecular mechanism underlying the effect of lipid metabolism on the phenotype and function of macrophages is still unclear, and the mechanism of association between AMD and cancer and COVID-19 has not been reported. The purpose of this study is to explore the interaction between lipid metabolism related genes, ferroptosis related genes and immunity in AMD, find out the key genes that affect the ferroptosis of AMD through lipid metabolism pathway and the molecular mechanism that mediates the action of macrophages, and find out the possible mechanism of lipid metabolism and potential co-therapeutic targets between AMD and cancer and COVID-19, so as to improve treatment decision-making and clinical results...

CO2 anesthesia is the most common method for immobilizing Drosophila for research purposes. But CO2 exposure has consequences-it can impact fertility, behavior, morphogenesis, and cytoskeletal dynamics. In this respect, Drosophila is an outstanding model for studying the impact of CO2 exposure on tissues. In this study we explored the response of intracellular pH (pHi) to a one-minute CO2 pulse using a genetically encoded, ubiquitously expressed pH sensor, tpHusion, to monitor pHi within a live, intact, whole fly...

OBJECTIVES: Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. METHODS: We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals...

Altered cholesterol, oxysterol, sphingolipid, and fatty acid concentrations are reported in blood, cerebrospinal fluid, and brain tissue of people with relapsing remitting multiple sclerosis (RRMS) and are linked to disease progression and treatment responses. CD4+ T cells are pathogenic in RRMS, and defective T cell function could be mediated in part by liver X receptors (LXRs) - nuclear receptors that regulate lipid homeostasis and immunity. RNA-sequencing and pathway analysis identified that genes within the 'lipid metabolism' and 'signalling of nuclear receptors' pathways were dysregulated in CD4+ T cells isolated from RRMS patients compared with healthy donors...

BACKGROUND: Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs...