Immunology & Cell Biology最新文献

T cells of the adaptive immune system recognize pathogens and malignantly transformed cells through a process called antigen presentation. During this process, peptides are displayed on major histocompatibility complex (MHC) class I and II molecules. Self-reactive T cells are typically removed or suppressed during T-cell development and through peripheral tolerance mechanisms, ensuring that only T cells recognizing peptides that are either absent or present in low abundance under normal conditions remain. This selective process allows T cells to respond to peptides derived from foreign proteins while ignoring those from self-proteins. However, T cells can also respond to peptides derived from proteins that have undergone post-translational modifications (PTMs). Over 200 different PTMs have been described, and while they are essential for protein function, localization and stability, their dysregulation is often associated with disease conditions. PTMs can affect the proteolytic processing of proteins and prevent MHC binding, thereby changing the repertoire of peptides presented on MHC molecules. However, it is also increasingly evident that many peptides presented on MHC molecules carry PTMs, which can alter their immunogenicity. As a result, the presentation of post-translationally modified peptides by MHC molecules plays a significant role in various diseases, as well as autoimmune disorders and allergies. This review will provide an overview of the impact of PTMs on antigen presentation and their implications for immune recognition and disease.

Role models play a crucial role in inspiring and guiding careers in science, offering tangible examples of success and resilience. Reflecting on my journey from a small town in southern Chile to leading a lab at Karolinska Institutet, I've learned that relatable role models are particularly impactful for overcoming imposter syndrome and fostering a sense of belonging in academia. Early in my career, I drew inspiration from peers and mentors, gradually building my confidence and embracing my strengths. Later, exposure to interdisciplinary role models expanded my horizons and shaped my approach to science. Now, as a PI, I see my role as both a coach and mentor, fostering a team dynamic that amplifies individual strengths. Success in science often stems from fearlessness, adaptability and a willingness to seize opportunities, even when the outcome is uncertain. My journey demonstrates that good scientists can come from anywhere, including a small town in southern Chile.

The need for climate action is becoming increasingly urgent, and research labs need to be part of the solution. Scientific labs consume large amounts of energy and water and produce significant waste. Globally, scientific research generates over 5.5 million tons of plastic waste annually, which is ~2% of the world's plastic waste. Recognizing the need for sustainability in research, the La Trobe Green Labs program leads this effort in Australia. Since receiving Australia's first “MyGreenLab” certification in 2021, a dedicated steering committee of volunteers has driven successful green initiatives at La Trobe University. The program ensures proper implementation of sustainable practices, enhanced safety and integration with existing operations. More importantly, these small changes will initiate wide-scale and long-term transformations that will improve research into more sustainable options for the future.

In this article, we discuss a recently published study by Gopee et al., who have unveiled a surprising role for macrophages in human prenatal skin development, extending far beyond their traditional immune function. By constructing a comprehensive multi-omics single-cell atlas of human prenatal skin, they demonstrate that innate immune cells play a key role in hair follicle formation, scarless wound healing and neurovascular development.

As a young scientist in Brazil, my journey began with a modest education in a public school system that often lacked the resources needed to provide students with comprehensive support. However, with persistence and determination, I successfully gained admission to the University of São Paulo, a prestigious institution and one of the top universities in Latin America. My research focuses on the relationship between the nervous and immune systems in psychosis, a topic I am deeply passionate about. In this piece, I will discuss the systemic issues within the Brazilian education and research systems and delve deeper into my own challenges and achievements as a young scientist in Brazil, sharing insights that can inspire others in similar situations.

Located in Brisbane's Northshore riverfront precinct, just meters from the iconic Brisbane River, is the new Vaxxas Biomedical Facility. Dr Imogen Bermingham is a Principal Scientist in the Formulation and Analytical Team at Vaxxas, an Australian biotech company focused on developing a needle-free vaccination technology. Here, we discuss her work at Vaxxas, highlighting the opportunities for translational research within the growing biotech industry landscape in Queensland, Australia. Dr Bermingham also reflects on her transition from academia to industry, leveraging her skill set and expanding her capabilities within the dynamic research environment at Vaxxas.

Undergraduate courses in immunology are content-heavy and combined with a new, complex vocabulary, can be an overwhelming subject for students. In-class active learning approaches have been found to improve understanding of difficult concepts in science, technology, engineering and mathematics (STEM) disciplines; however, many undergraduate courses maintain a high dependence on lecture-style teaching because of time constraints, content demands and student resistance. We designed an online, out-of-class activity, the “Life and Death of a T cell”, to complement a lecture on a complex immunological concept, T-cell development. Inspired by the “Choose Your Own Adventure” children's books, a fictional narrative was created in which students assume the role of a cell with a dream of becoming a helper T cell. Decision-making scenarios then prompt students to draw on their knowledge from the lecture to successfully navigate the steps of T-cell development. The activity was built on two platforms, Google Forms and H5P (HTML 5 Package), both of which are readily accessible and allow the inclusion of branching logic and the creation of a decision tree–based activity. An anonymous survey revealed that students found this interactive approach enjoyable, and their perceived understanding of the content significantly increased. Students appreciated the inclusion of a novel learning resource, with requests for similar activities to be developed for other immunological concepts. In conclusion, we developed a narrative-based, decision-making activity to complement a lecture on T-cell development. As an out-of-class activity, this style of learning approach can potentially capitalize on the benefits of active learning, while also overcoming barriers of student resistance.

Anti-CD19 Chimeric Antigen Receptor (CAR)-T cell therapies have shown promise for treating B cell malignancies, but the clinical outcome is influenced by both the CAR-T product and the patient's immune system. The role of γδ T cells in the context of CAR-T cell therapy remains poorly understood. This study investigates the transcriptional heterogeneity, clonal expansion and dynamics of γδ T cells in patients undergoing anti-CD19 CAR-T cell therapy. Longitudinal single cell multi-omics analysis was performed on γδ T cells from four patients receiving anti-CD19 CAR-T cell therapy. Single cell RNA-seq, antibody-based protein profiling (AbSeq) and full-length TCRγδ sequences revealed clonally expanded populations displaying plasticity in T cell differentiation, and temporal dynamics of large clones, suggesting ongoing expansion and differentiation. Clonally expanded γδ T cells had heterogeneous gene expression profiles, occupying seven transcriptionally distinct clusters. Analysis of chemokine markers indicated cluster-specific homing tendencies of circulating γδ T cells to peripheral tissues. We found unexpectedly high frequencies of Vδ1 and Vδ3 cells in the blood with distinct gene and protein expression profiles. This analysis provides insights into the dynamic and heterogeneous nature of γδ T cells following anti-CD19 CAR-T cell therapy, contributing valuable information for optimizing CAR-T cell therapies in B cell malignancies.

In science and academia, success is often shaped by both knowledge and networking. Reflecting on nearly two decades in academic research, I recount my experience as a postdoctoral immunologist returning to Australia with limited local connections and support. Upon re-establishing myself in Australia, I initially faced barriers that restricted my visibility and collaborations. A turning point came when personal challenges motivated me to actively network, leading to valuable collaborations and career opportunities. By initiating conversations with academic leaders and peers, I expanded my network and established numerous leadership roles, even as a “junior” postdoc through founding a symposium, engaging with an immunology society, volunteering on various academic and advocacy committees, contributing to public outreach and nationally advocating for gender equity in science. These experiences reinforced that networking is about fostering meaningful relationships and creating opportunities to grow professionally. I provide advice on how to increase your networks by volunteering at work, when attending conferences, through contributing to societies and building a social media presence. My journey highlights the importance of being proactive in building networks, which can open doors, amplify one's voice, and drive career advancement in science and academia.

Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required. We evaluated whether peripheral blood immune subsets and expression of clinically relevant immune checkpoint markers are associated with clinicopathologic features of BC. Peripheral blood mononuclear cells isolated from blood collected from 23 patients with BC and 9 age-matched unaffected-by-cancer control donors were assessed using a 21-parameter flow cytometry panel composed of markers of T, B, natural killer and myeloid populations and immune checkpoint markers. Patients with BC had significantly lower numbers of circulating CD19⁺ B cells and elevated circulating CD4⁺CD8⁺ T cells compared with the control cohort. Immune checkpoint markers programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) were elevated in the total peripheral immune cell population in patients with BC. Within the BC cohort, PD-1 expression in T and myeloid cells was elevated in muscle-invasive compared with non–muscle-invasive disease. In addition, elevated T, B and myeloid PD-1 cell surface expression was significantly associated with tumor stage, suggesting that measures of peripheral immune cell exhaustion may be a predictor of tumor progression in BC. Finally, positive correlations between expression levels of the various immune checkpoints both overall and within key peripheral blood immune subsets collected from patients with BC were observed, highlighting likely coregulation of peripheral immune checkpoint expression. The peripheral blood immunophenotype in patients with BC is altered compared with cancer-free individuals. Understanding this dysregulated immune profile will contribute to the identification of diagnostic and prognostic indicators to guide effective immune-targeted, personalized treatments.