Antibody-like recognition of a γδ T cell receptor toward a foreign antigen.

The antigen recognition principles of B cells and αβ T cells have been well described compared to those of the γδ T cell. By way of their specificity conferring receptor (γδTCR), γδ T cells can directly bind proteinaceous antigens. A known γδ T cell and B cell model antigen is phycoerythrin (PE), a light harvesting protein from rhodophytes and cyanobacteria.

Induction of the ISR by AB5 subtilase cytotoxin drives type-I IFN expression in pDCs via STING activation.

We demonstrate that exposure to the AB5 subtilase cytotoxin (SubAB) induces the unfolded protein response (UPR) in human peripheral blood mononuclear cells, concomitant with a proinflammatory response across distinct cell subsets. Notably, SubAB selectively induces type-I interferon (IFN) expression in plasmacytoid dendritic cells, acting synergistically with Toll-like receptor 7 stimulation. The induction of type-I IFN in response to SubAB relies on stimulator of interferon genes (STING) activation, coupled with protein synthesis inhibition mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) and phosphorylation of the eukaryotic translation initiation factor 2 subunit-alpha.

De Novo Protein Synthesis Occurs Through the Cytoplasmic Translation Machinery in Mammalian Spermatozoa.

The current hypothesis suggests that translation occurs in capacitated spermatozoa through mitochondrial ribosomes. Mitochondrial translation has several particularities, which rise some questions about how mitochondrial ribosomes can ensure sperm translation activity. Here, we aimed to elucidate if cytoplasmic translation occurs in mammalian spermatozoa.

Special Issue Titled "Advances in Biomass-Based Materials and Their Applications".

As the world faces a turning point where it is necessary to find effective replacements for oil-based products, new strategies must be pursued [...

Differential unfolded protein response regulation in KRAS silencing sensitive and innately resistant colorectal cancer cells.

Despite the development of mutant-selective KRAS inhibitors, colorectal cancer (CRC) responses remain limited, with stable disease and rapid recurrence being common outcomes. The molecular mechanisms enabling CRC cells to tolerate KRAS inhibition and ultimately develop resistance remain poorly understood. Here, we investigated early transcriptional and proteomic responses to KRAS silencing in 3D CRC cell line spheroid models, aiming to identify pathways associated with sensitivity or resistance to KRAS blockade.

Sensing mycobacteria through unconventional pathways.

Approximately one-quarter of the global population is estimated to be infected with Mycobacterium tuberculosis. New developments in vaccine design and therapeutics are urgently needed, particularly in the face of multidrug-resistant tuberculosis (TB). In this issue of the JCI, Sakai and colleagues used a multidisciplinary approach to determine that trehalose-6-monomycolate (TMM), a mycobacterial cell wall lipid, serves as a T cell antigen presented by CD1b.

Corrigendum: The role of dendritic cells in tertiary lymphoid structures: implications in cancer and autoimmune diseases.

[This corrects the article DOI: 10.3389/fimmu.2024.

Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes.

Background: Plasmacytoid dendritic cells (pDCs) play a key role in systemic sclerosis (SSc) pathophysiology. However, despite the recognised importance of metabolic reprogramming for pDC function, their metabolic profile in SSc remains to be elucidated. Thus, our study aimed to explore the metabolic profile of pDCs in SSc and their potential contribution to the disease.

Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation.

Background: Fibrosis remains a major complication in several chronic diseases, including systemic sclerosis (SSc). Plasmacytoid dendritic cells (pDCs) are innate immune cells that play a key role in the development of fibrosis in SSc patients, through still poorly defined mechanisms. Interestingly, endoplasmic reticulum (ER) stress signaling pathways are dysregulated in pDCs from patients with SSc, but their contribution to fibrosis remains unclear.

Insulin resistance compromises midbrain organoid neuronal activity and metabolic efficiency predisposing to Parkinson's disease pathology.

Growing evidence indicates that type 2 diabetes (T2D) is associated with an increased risk of developing Parkinson's disease (PD) through shared disease mechanisms. Studies show that insulin resistance, which is the driving pathophysiological mechanism of T2D plays a major role in neurodegeneration by impairing neuronal functionality, metabolism and survival. To investigate insulin resistance caused pathological changes in the human midbrain, which could predispose a healthy midbrain to PD development, we exposed iPSC-derived human midbrain organoids from healthy individuals to either high insulin concentration, promoting insulin resistance, or to more physiological insulin concentration restoring insulin signalling function.

The Importance of Cellular Therapy in the Clinical Case of a Young Man With a Challenging Precursor B-cell Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) poses a significant challenge due to its high relapse rate despite initial chemotherapy. Cell therapy plays an important and promising role in refractory ALL cases. The aim is to present a complex case of a 20-year-old male patient with relapsed ALL and to explore the different therapeutic options of cellular therapy - allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, and chimeric antigen receptor T - detailing the collection, processing, and infusion, as well as the associated complications and management strategies.

Addressing Venous Extravasation, a Concern in Intravenous Iron Administration.

Intravenous iron is commonly used to treat anemia related to chronic illnesses, but venous extravasation, an uncommon side effect of intravenous iron, can result in persistent skin discoloration. This report presents the case of a female patient who experienced venous extravasation following intravenous iron administration, with data collected from her patient record. Although venous extravasation is a rare adverse effect, it is important for both patients and healthcare providers to recognize this potential complication.

An Unexpected Case of Generalized Tetanus.

Tetanus is a disease of the nervous system caused by a toxin produced by , an anaerobe found in high concentrations in the soil. The occurrence of tetanus is related to contaminated traumatic wounds, and most patients have had some failure in their immunization. However, there are rare case reports of generalized tetanus in patients with proper vaccination schemes who failed to receive appropriate prophylaxis after high-risk exposure.

The role of dendritic cells in tertiary lymphoid structures: implications in cancer and autoimmune diseases.

Tertiary Lymphoid Structures (TLS) are organized aggregates of immune cells such as T cells, B cells, and Dendritic Cells (DCs), as well as fibroblasts, formed postnatally in response to signals from cytokines and chemokines. Central to the function of TLS are DCs, professional antigen-presenting cells (APCs) that coordinate the adaptive immune response, and which can be classified into different subsets, with specific functions, and markers. In this article, we review current data on the contribution of different DC subsets to TLS function in cancer and autoimmunity, two opposite sides of the immune response.

Antitumoral Activity and Metabolic Signatures of Dichloroacetate, 6-Aminonicotinamide and Etomoxir in Breast-Tumor-Educated Macrophages.

Pharmacological targeting of metabolic pathways represents an appealing strategy to selectively kill cancer cells while promoting antitumor functions of stromal cells. In this study, we assessed the effectiveness of 13 metabolic drugs (MDs) in steering generated breast tumor-educated macrophages (TEMs) toward an antitumoral phenotype. For that, the production of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α), two important regulators of tumor progression, was evaluated.

The Role of Liquid Biopsy in Gastroenteropancreatic Neuroendocrine Neoplasms.

Neuroendocrine neoplasms incidence has been increasing, arising the need for precise and early diagnostic tools. Liquid biopsy (LB) offers a less invasive alternative to tissue biopsy, providing real-time molecular information from circulating tumour components in body fluids. The aim of this review is to analyse the current evidence concerning LB in NENs and its role in clinical practice.

HPV and Lung Cancer: A Systematic Review.

This systematic review aims to explore the diagnostic criteria, epidemiology, etiology, and prognosis of Human Papillomavirus (HPV) infection in lung cancer. This PRISMA-guided review searched the PubMed and Embase databases for "lung cancer AND HPV" on 10 June 2023, filtering human subject papers. A total of 97 studies encompassing 9098 patients worldwide, revealing varied HPV infection rates in lung cancer, ranging from 0% to 69%, were analyzed.

Direct recognition of an intact foreign protein by an αβ T cell receptor.

αβ T cell receptors (αβTCRs) co-recognise antigens when bound to Major Histocompatibility Complex (MHC) or MHC class I-like molecules. Additionally, some αβTCRs can bind non-MHC molecules, but how much intact antigen reactivities are achieved remains unknown. Here, we identify an αβ T cell clone that directly recognises the intact foreign protein, R-phycoerythrin (PE), a multimeric (αβ)γ protein complex.

The surveillance of viral infections by the unconventional Type I NKT cell.

Type I NKT cells, also known as Invariant Natural Killer T (iNKT) cells, are a subpopulation of unconventional, innate-like T (ILT) cells which can proficiently influence downstream immune effector functions. Type I NKT cells express a semi-invariant αβ T cell receptor (TCR) that recognises lipid-based ligands specifically presented by the non-classical cluster of differentiation (CD1) protein d (CD1d) molecule. Due to their potent immunomodulatory functional capacity, type I NKT cells are being increasingly considered in prophylactic and therapeutic approaches towards various diseases, including as vaccine-adjuvants.

Lipidomic scanning of self-lipids identifies headless antigens for natural killer T cells.

To broadly measure the spectrum of cellular self-antigens for natural killer T cells (NKT), we developed a sensitive lipidomics system to analyze lipids trapped between CD1d and NKT T cell receptors (TCRs). We captured diverse antigen complexes formed in cells from natural endogenous lipids, with or without inducing endoplasmic reticulum (ER) stress. After separating protein complexes with no, low, or high CD1d-TCR interaction, we eluted lipids to establish the spectrum of self-lipids that facilitate this interaction.

Refractory Fetal and Neonatal Supraventricular Tachycardia Associated With Mitral Valve Mass.

Primary cardiac tumors in children are rare and mostly benign but can cause significant cardiovascular complications, including arrhythmias. We present a rare case of fetal and neonatal refractory supraventricular tachycardia linked to a probable mitral valve hemangioma, resulting in severe neonatal and maternal morbidity. Despite challenges, pharmacological therapy ultimately successfully managed the condition, highlighting the importance of individualized treatment in such complex cases.

Modeling 3D Tumor Invasiveness to Modulate Macrophage Phenotype in a Human-Based Hydrogel Platform.

The immune system is a pivotal player in determining tumor fate, contributing to the immunosuppressive microenvironment that supports tumor progression. Considering the emergence of biomaterials as promising platforms to mimic the tumor microenvironment, human platelet lysate (PLMA)-based hydrogel beads are proposed as 3D platforms to recapitulate the tumor milieu and recreate the synergistic tumor-macrophage communication. Having characterized the biomaterial-mediated pro-regenerative macrophage phenotype, an osteosarcoma spheroid encapsulated into a PLMA hydrogel bead is explored to study macrophage immunomodulation through paracrine signaling.