Mucosal associated invariant T cells (MAIT cells) are a group of evolutionarily conserved and unconventional innate-like T cell subsets. Since first defined in 2003, it has been found to be involved in physiological and pathological process. The study is aimed to explore the research content, present hotspots and future trends of MAIT cells through bibliometric approach. The publication was searched using Web of Science Core Collection database (WoSCC). The bibliometrix package in R was used for data extraction and quantitative analysis of bibliometrics and scientometrics. A cloud plot was generated to display the hotspots of WoSCC keywords in MAIT cell researches. Thematic analysis and trend topics map were conducted to appraise the maturity and development trend of topics in MAIT cell studies. The collaboration network, including author collaboration and affiliation collaboration, were visualized by using VOSviewer. A total of 1041 related publications obtained from WoSCC were analyzed. It is found that nearly 10 years researches on MAIT cells surging with the US being the major producer. The groups of James McCluskey and Jamie Rossjohn contributed most to the research of MAIT cells. “Frontiers in Immunology” and “Journal of Immunology” were the most prolific. Activation and function are the hotspots of the researches of MAIT cells. Applying advanced sequencing technology to explore the interaction of MAIT cells with microbiota in diseases may be the research trend.The bibliometric analysis provides novel and useful data for the MAIT research scientific community, which was conducive to elucidating MAIT cells more effectively and intuitively.

Undernutrition significantly compromises immune function, particularly in vulnerable populations. This study explores the impact of undernutrition on apoptotic pathways and thymocyte development in rats, shedding light on potential mechanisms underlying immune suppression. This study investigates the effects of undernutrition on apoptotic pathways and thymocyte development in rat models. Undernutrition was induced by competitive suckling, leading to weight deficits of 40% or more. Thymocytes were analyzed using flow cytometry to assess mitochondrial function, caspase activation, and subpopulation alterations among thymocytes, providing insights into the mechanisms underlying immune suppression due to undernutrition. The undernourished rats showed reduced thymus weight, modifications in thymocyte subpopulations, and diminished mitochondrial potential. The analysis of caspase activation unveiled a significant role of caspase 9 in early apoptosis, suggesting a link between mitochondrial dysfunction and the apoptosis of thymocytes induced by undernutrition. These alterations in thymic structure and apoptotic pathways align with previous studies, emphasizing the vulnerability of the thymus to undernutrition. The alterations observed in thymocyte subpopulations and caspase activation patterns provide insights into the intricate relationship between undernutrition, thymic function, and immune suppression. This study contributes to understanding how undernutrition during lactation affects thymic function and apoptotic pathways. These findings highlight the critical necessity for additional research to unravel the underlying mechanisms and identify potential therapeutic interventions to alleviate the detrimental impact of undernutrition on thymic development and immune function.

The αLβ2 integrin LFA-1 plays a key role in T-cell adhesion to the endothelial vasculature and migration into both secondary lymphoid organs and peripheral tissues via interactions with its target protein ICAM-1, but the pathways that regulate LFA-1-mediated T-cell polarity and migration are not fully understood. In this study we screened two RNAi libraries targeting G protein-coupled receptors (GPCR)/GPCR-associated proteins and kinases in a HuT-78 T-cell line model of LFA-1-stimulated T cell migration. Based on staining of the actin cytoskeleton, multiple parameters to measure cell morphology were used to assess the contribution of 1109 genes to LFA-1-mediated T cell polarity and migration. These RNAi screens identified a number of both novel and previously identified genes that either increased or decreased the polarity and migratory capacity of these cells. Following multiparametric analysis, hierarchical clustering and pathway analysis, three of these genes were characterised in further detail using primary human T-cells, revealing novel roles for the heterotrimeric G protein subunit Gβ1 and casein kinase 2 in LFA-1-mediated T-cell polarity and migration in-vitro. Our studies also highlighted a new role for ICAP-1, an adaptor protein previously described to be associated with β1 integrins, in β2 integrin LFA-1-directed migration in T-cells. Knockdown of ICAP-1 expression in primary T cells revealed a role in cell polarity, cell velocity and transmigration towards SDF-1 for this adaptor protein. This study therefore uncovers new roles for GPCR/GPCR-associated proteins and kinases in T-cell migration and provides potential novel targets for modulation of the T-cell immune response

Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial abnormalities and increased reactive oxygen species (ROS) levels in lymphoblastoid cell lines (LCLs) derived from RNASEH2B- and RNASEH2A-mutated AGS patients. On this background, we turned our attention to metformin, the first-choice drug for type 2 diabetes, as a possible treatment acting on the oxidative stress condition in RNASEH2-mutant AGS cells. By means flow cytometry; we reported that metformin treatment significantly decreases ROS production in RNASEH2B- and RNASEH2A-mutated AGS LCLs. Of note, metformin treatment reduces the green JC-1 monomeric signal and, concurrently, increases the red JC-1 signal in both mutated LCLs, accounting for a restoration of the mitochondrial membrane potential. Immunofluorescence staining shows a decrease in 8-oxoG levels only in RNASEH2B- mutated AGS LCLs. Finally, the significant upregulation of FOXO3, cytochrome C somatic (CYCS) and superoxide dismutase 2 (SOD2) mRNA levels in RNASEH2B-mutated AGS LCLs after metformin treatment, points to FOXO3 signaling as a possible mechanism to reduce oxidative stress. In conclusion, even if these pilot results need to be confirmed on a larger cohort, we shed light on metformin as a valid approach to ameliorate the oxidative stress-related inflammatory condition in AGS patients.

The Gastroenterology Immunology Neuroscience (GIN) Discovery Program represents a new model for research that overcomes the limitations imposed by traditional ‘research silos’ in medical science. By adopting a cross-disciplinary, highly-integrated approach, the GIN Program unites the fields of gastroenterology, immunology, and neuroscience to comprehensively address chronic health challenges. This initiative not only bridges the gaps between basic science, clinical research, and patient care but also emphasises the importance of diversity in ideas, perspectives, and approaches when fostering innovation. The program’s organic, bottom-up growth strategy has facilitated the formation of a vibrant, interdisciplinary community, captivating attention from both national and international institutions. With a vision to create effective therapeutic solutions and pioneer advancements in gut-immune-brain axis research, the GIN Program exemplifies the power of interdisciplinary collaboration. This innovative commitment to change the landscape of medical research aims to inspire similar models that prioritise open communication, mutual respect, and a commitment to groundbreaking science.

CD8+ T cells recognising their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide-MHC (pMHC) complex. Advances in single-cell sequencing have increased accessibility towards identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8+ T cell population with specificity for a hepatitis C virus (HCV)-derived HLA class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent prior to infection and underwent expansion and stable maintenance for at least two years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterised by an unusually long dissociation time (half-life = 794 seconds and koff = 5.73×10-4) for its target antigen when compared to previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggest that high-affinity TCR-pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalised immunotherapies.

Individuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared to people with higher SES. Age, sex, host genetics, smoking, and Cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the Milieu Intérieur project, a study of 1,000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo-rating system using socioeconomic features such as education, income, and household to objectively rank SES in the 1,000 donors. We observed sex specific SES associations, such as females with a low SES having significantly higher frequency of CMV seropositivity compared to high SES females, and males from a low SES having significantly higher frequency of active smoking compared to high SES males. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex-stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES-dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind socioeconomic status effects on immune responses and ultimately disease.

This journey traces the transition from a brief dentistry stint to a neuroimmunology exploration. The narrative unfolds through academic pursuits at the University of São Paulo, Brazil, and subsequent doctoral studies, reflecting on the initial idealism that shaped the pursuit of academia. An unexpected postdoctoral experience at the Centre de Physiopathologie de Toulouse Purpan in France introduced me to immunology, leading to an unexpected passion. Here, I explore uncertainties, decisions, and a pivotal move to Belgium, where collaboration with Adrian Liston at VIB-KU Leuven marked a maturity phase. Amid personal milestones like pregnancy and the challenges of balancing parenthood with a burgeoning career, I would like to highlight the crucial role of support systems and a thriving research environment. My journey so far culminates in the establishment of a lab, the pursuit of a permanent position, and the appointment as an assistant professor at KU Leuven.

Effective vaccines have reduced SARS-CoV-2 morbidity and mortality; however, the elderly remain the most at risk. Understanding how vaccines generate protective immunity, and how these mechanisms change with age is key for informing future vaccine design. Cytotoxic CD8+ T cells are important for killing virally infected cells, and vaccines that induce antigen specific CD8+ T cells in addition to humoral immunity provide an extra layer of immune protection. This is particularly important in cases where antibody titres are sub-optimal, as can occur in older individuals. Here, we show that in aged mice, spike-epitope specific CD8+ T cells are generated in comparable numbers to younger animals after ChAdOx1 nCoV-19 vaccination, although phenotypic differences exist. This demonstrates that ChAdOx1 nCoV-19 elicits a good CD8+ T cell response in older bodies, but that typical age-associated features are evident on these vaccine reactive T cells.