Immune development

Obesity-induced chronic low-grade inflammation, also known as metaflammation, results from alterations of the immune response in metabolic organs and contributes to the development of fatty liver diseases and type 2 diabetes. The diversity of tissue-resident leukocytes involved in these metabolic dysfunctions warrants an in-depth immunophenotyping in order to elucidate disease etiology. Here, we present a 30-color, full spectrum flow cytometry panel, designed to (i) identify the major innate and adaptive immune cell subsets in murine liver and white adipose tissues and (ii) discriminate various tissue-specific myeloid subsets known to contribute to the development of metabolic dysfunctions...

Controlling the end-groups of biocompatible polymers is crucial for enabling polymer-based therapeutics and nanomedicine. Typically, end-group diversification is a challenging and time-consuming endeavor, especially for polymers pre-pared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end-group diversification approach for poly(2-oxazoline)s (POx), enabling quick and reliable production of hetero-telechelic polymers to facilitate POxylation. The approach relies on the careful tuning of reaction parameters to establish differential reactivity of a pentafluorobenzyl initiator fragment and the living oxazolinium chain-end, allowing the selective introduction of N-, S-, O-nucleophiles via the termination of the polymerization, and a consecutive nucleophilic para-fluoro substitution...

Atherosclerosis remains a leading cause of cardiovascular disease (CVD) globally, with the complex interplay of inflammation and lipid metabolism at its core. Recent evidence suggests a role of B cells in the pathogenesis of atherosclerosis; however, this relationship remains poorly understood, particularly in the context of HIV. We review the multifaceted functions of B cells in atherosclerosis, with a specific focus on HIV. Unique to atherosclerosis is the pivotal role of natural antibodies, particularly those targeting oxidized epitopes abundant in modified lipoproteins and cellular debris...

Triatomines (kissing bugs) and tsetse flies (genus: Glossina) are natural vectors of Trypanosoma cruzi and Trypanosoma brucei, respectively. T. cruzi is the causative agent of Chagas disease, endemic in Latin America, while T. brucei causes African sleeping sickness disease in sub-Saharan Africa. Both triatomines and tsetse flies are host to a diverse community of gut microbiota that co-exist with the parasites in the gut. Evidence has shown that the gut microbiota of both vectors plays a key role in parasite development and transmission...

Hepatocellular carcinoma is one of the most common cancers worldwide. Despite progress in treatment, recurrence after radical treatment is common, and the prognosis remains poor for patients with advanced disease. Therefore, there is a need to identify prognostic and predictive factors for the response to therapy or more intensive surveillance or treatment. Because the tumor microenvironment plays a crucial role in the development of cancer and metastasis, it is a crucial need to understand processes that are involved in carcinogenesis...

Designing and developing photosensitizers with cell membrane specificity is crucial for achieving effective multimodal therapy of tumors compared to other organelles. Here, we designed and screened a photosensitizer CM34 through donor/receptor regulation strategies, and it is able to achieve long-retention cell membrane targeting. It is not only an extremely excellent cell membrane targeted tumor theranostic agent, but also found to be a promising potential immune activator. Specifically, CM34 with a larger intramolecular twist angle is more likely to form larger aggregates in aqueous solutions, and the introduction of cyanide group also enhances its interaction with cell membranes, which were key factors hindering molecular penetration of the cell membrane and prolonging its residence time on the cell membrane, providing conditions for further membrane targeted photodynamic therapy...

Extracellular vesicles (EVs) originating from cancer cells incorporate various critical biomolecules that can aid in early cancer diagnosis. However, the rapid analysis of these micro vesicles remains challenging due to their nano-scale size and overlapping dimensions, hindering sufficient capture in terms of quantity and purity. In this study, an acoustofluidic device was developed to enhance the yield of immune-captured EVs. The channel of the device was modified with degradable gelatin nanoparticles (∼220 nm) to increase the surface roughness, and subsequently treated with CD63 antibodies...

Acute invasive fungal sinusitis (AIFS) classically presents as an aggressive fungal infection that can spread beyond its origin in the sinuses in immunocompromised patients. Although there have been reports of AIFS in immunocompetent, non-diabetic patients, it is extremely rare and the true mechanism behind it is unknown. A thirty-eight year old immunocompetent, non-diabetic woman underwent bilateral ESS for chronic rhinosinusitis with nasal polyps at a tertiary care center and post-operatively developed AIFS...

The co-occurrence of myasthenia gravis (MG) and paroxysmal nocturnal hemoglobinuria (PNH) is rare; only one case has been published so far. We report a 63-year-old Caucasian female patient who was diagnosed with MG at the age of 43. Thymoma was also detected, and so it was surgically resected, which resulted in reasonable disease control for nearly 20 years. Slight hemolysis began to emerge, and then myasthenia symptoms progressed, so immunosuppressive therapy was started. Due to progressive disease and respiratory failure, the patient underwent plasmapheresis, and ventilatory support was stopped...

Chronic Obstructive Pulmonary Disease (COPD) is a disease of the lungs characterized by chronic airflow obstruction. Individuals with preserved ratio impaired spirometry (PRISm) may be at risk for developing COPD. This study aimed to characterize PRISm and COPD patients in terms of their immune response and endocrine profile to identify differences extending beyond lung function. The participants performed the clinical assessment, pulmonary function test, and blood collection to determine serum hormone levels and concentrations of cytokine...

The activation of CD40-mediated signaling in antigen-presenting cells is a promising therapeutic strategy to promote immune responses against tumors. Most agonistic anti-CD40 antibodies currently in development require the Fcγ-receptor (FcγR)-mediated crosslinking of CD40 molecules for a meaningful activation of CD40 signaling but have limitations due to dose-limiting toxicities. Here we describe the identification of CD40 antibodies which strongly stimulate antigen-presenting cells in an entirely FcγR-independent manner...

The vast majority of antibodies generated against a virus will be non-neutralising. However, this does not denote an absence of protective capacity. Yet, within the field, there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, NAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bNAbs). More recently, a focus on non-neutralising antibodies (nNAbs), or neutralisation-independent effects of NAbs, has emerged...

BACKGROUND: One of the mechanisms regulating the biological activity of tumor necrosis factor (TNF) in cells is the co-expression of TNFR1/TNFR2 receptors. A model with a differential level of receptor expression is required to evaluate the contribution of these mechanisms. AIM: The development of a cellular model to compare the effects of TNF on cells depending on the presence of both receptors and TNFR2 alone. METHODS: TNFR1 absence modifications of ZR-75/1 and K-562 cell lines were obtained by TNFR1 knockout...

The effects of PM2.5 on human health fluctuate greatly among various age groups, influenced by a range of physiological and immunological reactions. This paper compares the pathogenesis of the disease caused by PM2.5 in people of different ages, focusing on how children, adults, and the elderly are each susceptible to it because of differences in their bodies. Regarding children, exposure to PM2.5 is linked to many negative consequences. These factors consist of inflammation, oxidative stress, and respiratory problems, which might worsen pre-existing conditions and potentially cause neurotoxicity and developmental issues...

BACKGROUND: Colitis was the third most common immune-related adverse effect in melanoma patients treated with immune-checkpoint inhibitor (ICI). With the limitation of real-world data in the UK population, this study was conducted in a UK hospital where a fresh colitis guidance was introduced to evaluate the overall grading (OG) to assess colitis severity and guide the treatment. AIMS: This study aimed to investigate colitis severity by Common Terminology Criteria for Adverse Events (CTCAE) grade and overall grade at time of presentation...

The field of neuroimmunology is quickly expanding and, as the primary immune cell of the brain, microglia are truly in the spotlight. In 2023, the number of microglia related articles published on PubMed rose to 5152. This number has consistently increased year on year and has more than doubled since 2013, as we begin to appreciate the role of microglia in brain development, health and disease. The year 2023 continued to bring new important discoveries, extending our knowledge of microglia biology. This image was created in BioRender...

Total joint arthroplasty (TJA) is a surgical procedure, in which parts of damaged joints are removed and replaced with a prosthesis. The main indication of TJA is osteoarthritis, and the volume of TJA is rising annually along with the increase of aged population. Hip and knee are the most common joints, in which TJAs are performed. The TJA prosthesis is composed of metal, plastic, or ceramic device. Even though TJA is the most successful treatment for end-stage osteoarthritis, it is associated with various complications, and periprosthetic joint infection (PJI) is the most serious complication after TJA...

Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders...

Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression despite tecovirimat treatment. Treatment resistance can be due to acquired mpox strain mutations, most often occurring in an immunocompromised host. We present the case of a male with AIDS who developed disseminated treatment-resistant mpox infection complicated by superimposed bacterial and fungal infections. His orthopoxvirus polymerase chain reaction result remained positive despite treatment with 4 weeks of oral tecovirimat and 3 doses of intravenous cidofovir...

BACKGROUND: There is growing evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of immune mediated neuropathies like chronic inflammatory demyelinating polyneuropathy (CIDP), but the impact of SARS-CoV-2 vaccination and COVID-19 infection on genetic disorders such as Charcot-MarieTooth (CMT) remains unclear. CASE PRESENTATION: A 42-year-old male with occulted CMT neuropathy type lA (CMT1A) who developed limb numbness and weakness after the second SARS-CoV-2-vaccination was confirmed by identifying characteristic repeats in the p11...