Immunology & Cell Biology最新文献

Macrophages are a key cell type of the innate immune system and are involved at all steps of inflammation: (i) they present antigens to initiate inflammation, (ii) they clear up foreign bodies through phagocytosis and (iii) they resolve inflammation by removing or deactivating mediator cells. Many subtypes of macrophages have been identified, classified by their niche and/or embryonic origin. In order to better develop therapies for conditions with macrophage dysfunction, it is crucial to decipher potential sex differences in key physiological mediators of inflammation so that treatment efficacy can be ensured regardless of biological sex. Here, we conduct a meta-analysis approach of transcriptomics data sets for male vs. female mouse macrophages across 8 niches to characterize conserved sex-dimorphic pathways in macrophages across origins and niches. For this purpose, we leveraged new and publicly available RNA-sequencing data sets from murine macrophages, preprocessed these datasets and filtered them based on objective QC criteria, and performed differential gene expression analysis using sex as the covariate of interest. Differentially expressed (DE) genes were compared across data sets and macrophage subsets, and functional enrichment analysis was performed to identify sex-specific functional differences. Consistent with their presence on the sex chromosomes, three genes were found differentially expressed across datasets (i.e. Xist, Eif2s3y and Ddx3y). More broadly, we found that female-biased pathways across niches are more consistent than male-biased pathways, specifically relating to the extracellular matrix. Our findings increase our understanding of transcriptional similarities across macrophage niches and underscore the importance of including sex as a biological variable in immune-related studies.

The field of immunology in Chile has evolved remarkably over the past few decades, from a nascent discipline to a dynamic and rapidly developing community with significant international visibility. In this commentary, we, Fabiola Osorio and María Rosa Bono, offer personal reflections on the challenges and opportunities facing Chile's immunology community. As researchers who both returned to Chile after extensive training abroad, we have seen the dynamic nature of the Immunology field within our country. Our opinions also arise from our experiences as past presidents of the Chilean Association of Immunology (ASOCHIN; 2016–2019 MRB; 2019–2021 FO), the main scientific society congregating immunology researchers in Chile, where we have witnessed firsthand the growth of the local immunological community. Our testimonies and those of our colleagues highlight the resilience, creativity and collaborative spirit that have allowed Chile to carve out its place in global immunology.

In this article for the Highlights of 2024 Series, we discuss recent discoveries in Treg immunometabolism, which reveal how inflammatory niches alter Treg fate and function through distinct metabolic cues. Key findings include IL-21-driven mitochondrial dysfunction, lactate-enhanced OXPHOS via MGAT1, sphingolipid-dependent Treg differentiation in tumors, ferroptosis susceptibility under high-fat diets, and sex-specific adipose Treg subsets modulating glucose homeostasis. Together, these insights highlight potential metabolic targets to restore Treg function in inflammatory diseases and cancer.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU), significantly impacts quality of life. Despite significant advances in the management of the conditions, responses to treatments vary greatly, and this is due partly to our natural genetic variation. Here we will review the evidence for whether single nucleotide polymorphisms (SNPs) have the potential to guide treatment decisions for people with IBD. We will first consider SNPs that exhibit strong associations with IBD pathogenesis and their relevance to epithelial barrier integrity, cytokine production, and immune system function. Then, we will cover those SNPs implicated in altering response to our various current IBD therapeutics, including the recently implemented drugs ustekinumab and tofacitinib. Finally, we will explore lesser-known SNPs that exhibit complex relationships with the disease and which may be undervalued as pharmacogenetic tools. Overall, it will be demonstrated that SNPs associated with IBD pathology are largely distinct from those predicting response to treatments and that new discoveries of clinically useful tools can be expected from therapy-focused investigations. Given the growing list of treatments available, we argue that beneficial personalization of treatments based on SNPs is still underutilized.

In this article for the “Highlights of 2024” Series, we discuss findings by our group and others that the Alzheimer's disease (AD) risk genetic variant apolipoprotein E ε4 (APOE4) is associated with peripheral immune dysregulation and chronic inflammation. We hypothesize that this leads to AD development via proinflammatory immune cells attacking the blood–brain barrier (BBB) to weaken it. Immune cells then infiltrate into the brain where they interact with brain cells to drive neuroinflammation, neurodegeneration, and AD pathology.

In this Research Highlight, we explore 5 influential basic and translational articles published in 2024 that shed light on the biology of age-associated B cells (ABCs) and their emerging role in autoimmunity.

The path to becoming an academic researcher is winding. The trajectories and landscapes of academic success may mean many different things to each of us. There is no clear or direct path anymore. Here, I share with you my journey, giving important insights I have gathered over the years, defining what parts of this career make it worthwhile.

Collectively, 2024 has significantly increased the wealth of knowledge regarding antibody-secreting cell heterogeneity in health and disease. This ‘Highlights of 2024’ article discusses key studies contributing to the understanding of how tissue residency and disease state influence the transcriptional programming of antibody-secreting cell phenotypes.

Regulation of cellular metabolism is a central element governing the fate and function of T cells. However, the in vivo metabolic characteristics of rare cells, such as nonlymphoid tissue T cells, are poorly understood because of experimental limitations. Most techniques measuring cell metabolism require large cell numbers. The recent SCENITH method allows for studying the metabolism of rare cells by flow cytometry. However, this technique requires cells to be isolated and cultured ex vivo, which may alter their metabolism. Here, we propose a new experimental approach, called in vivo SCENITH, to investigate the cellular metabolism of T cells in vivo at a steady state in the spleen and lungs. For this purpose, we administered the metabolic modulators directly in mice, instead of applying these reagents ex vivo, as in the classical SCENITH method. Whereas ex vivo manipulation impacted the viability and phenotype of T cells, this toxic effect was not observed in the in vivo SCENITH. We observed that conventional and regulatory T cells shared similar metabolic profiles. Importantly, whereas spleen T cells used both oxidative phosphorylation and glycolysis, the metabolism of T cells in the lungs was mainly based on oxidative phosphorylation. Finally, metabolic inhibitors that interfere with protein translation and energy availability downregulated Foxp3 expression in regulatory T cells. These results describe an expansion of SCENITH that allows to measure the metabolic profile of rare cells in vivo, revealing a high dependence on oxidative phosphorylation of lung T cells.

The microscopic world of intracellular bacteria is rarely communicated to non-scientists. By participating in the Sensory Science Exhibition, held at St Catharine's College, University of Cambridge as part of the Cambridge Festival, we sought to address this problem by creating a 3D mammalian cell with model bacteria, including Salmonella enterica, Chlamydia trachomatis and Orientia tsutsugamushi. By hijacking eukaryotic host cellular machinery and avoiding detection, these bacteria orchestrate their survival and replication within host cells. This tactile display aimed to guide participants through key aspects of intracellular bacterial life cycles such as host cell entry, Salmonella type three secretion system (T3SS) protein secretion, O. tsutsugamushi trafficking along microtubules, and C. trachomatis replication within an inclusion. We summarize our experiences in this report. We hope our multisensory conceptualization of intracellular bacteria provided inclusive and easy-to-understand communication of complex science concepts to the general public with modalities also accessible to the low-vision and blind communities.