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.

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.

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.

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.

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 CD4CD8 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.

T-cell-mediated therapeutic strategies are the most potent effectors of cancer immunotherapy. However, an essential barrier to this therapy in solid tumors is disrupting the anti-cancer immune response, cancer-immunity cycle, T-cell priming, trafficking and T-cell cytotoxic capacity. Thus, reinforcing the anti-cancer immune response is needed to improve the effectiveness of T-cell-mediated therapy. Tumor-associated protease ADAM10, endothelial cells (ECs) and cytotoxic CD8 T cells engage in complex communication via adhesion, transmigration and chemotactic mechanisms to facilitate an anti-cancer immune response. The precise impact of ADAM10 on the intricate mechanisms underlying these interactions remains unclear. This paper broadly explores how ADAM10, through different routes, influences the efficacy of T-cell-mediated therapy. ADAM10 cleaves CD8 T-cell-targeting genes and impacts their expression and specificity. In addition, ADAM10 mediates the interactions of adhesion molecules with T cells and influences CD8 T-cell activity and trafficking. Thus, understanding the role of ADAM10 in these events may lead to innovative strategies for advancing T-cell-mediated therapies.

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.

In this article, we discuss new findings which suggest that type I regulatory T (Tr1) cells can interfere with cancer vaccine efficacy in mice by exerting strong regulatory control over antitumor immune responses.

Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges. This study aimed to harness induced pluripotent stem cell (iPSC) technology to provide a consistent and scalable source of NK cells, overcoming the limitations of traditional sources and enhancing the potential for cancer immunotherapy applications. We developed human placental-derived iPSC lines using reprogramming techniques. Subsequently, an optimized two-step differentiation protocol was introduced to generate high-purity NK cells. Initially, iPSCs were differentiated into hematopoietic-like stem cells using spin-free embryoid bodies (EBs). Subsequently, the EBs were transferred to ultra-low attachment plates to induce NK cell differentiation. iPSC-derived NK (iNK) cells expressed common NK cell markers (NKp46, NKp30, NKp44, CD16 and eomesodermin) at both RNA and protein levels. iNK cells demonstrated significant resilience to cryopreservation and exhibited enhanced cytotoxicity. The incorporation of a chimeric antigen receptor (CAR) construct further augmented their cytotoxic potential. This study exemplifies the feasibility of generating iNK cells with high purity and enhanced functional capabilities, their improved resilience to cryopreservation and the potential to have augmented cytotoxicity through CAR expression. Our findings offer a promising pathway for the development of potential cellular immunotherapies, highlighting the critical role of iPSC technology in overcoming challenges associated with traditional NK cell sources.

The humoral response is complex and involves multiple cellular populations and signaling pathways. Bacterial and viral infections, as well as immunization regimens, can trigger this type of response, promoting the formation of microanatomical cellular structures called germinal centers (GCs). GCs formed in secondary lymphoid organs support the differentiation of high-affinity plasma cells and memory B cells. There is growing evidence that the quality of the humoral response is influenced by genetic variants. Using 12 genetically divergent mouse strains, we assessed the impact of genetics on GC cellular traits. At steady state, in the spleen, lymph nodes and Peyer's patches, we quantified GC B cells, plasma cells and follicular helper T cells. These traits were also quantified in the spleen of mice following immunization with a foreign antigen, namely, sheep red blood cells, in addition to the number and size of GCs. We observed both strain- and organ-specific variations in cell type abundance, as well as for GC number and size. Moreover, we find that some of these traits are highly heritable. Importantly, the results of this study inform on the impact of genetic diversity in shaping the GC response and identify the traits that are the most impacted by genetic background.

Chronic wounds significantly burden health care systems worldwide, requiring novel strategies to ease their impact. Many physiological processes underlying wound healing are well studied but the role of mast cells remains controversial. Mast cells are innate immune cells and play an essential role in barrier function by inducing inflammation to defend the host against chemical irritants and infections, among others. Many mast cell-derived mediators have proposed roles in wound healing; however, in vivo evidence using mouse models has produced conflicting results. Recently, studies involving more complex wound models such as infected wounds, diabetic wounds and wounds healing under psychological stress suggest that mast cells play critical roles in these processes. This review briefly summarizes the existing literature regarding mast cells in normal wounds and the potential reasons for the contradictory results. Focus will be placed on examining more recent work emerging in the last 5 years that explores mast cells in more complex systems of wound healing, including infection, psychological stress and diabetes, with a discussion of how these discoveries may inspire future work in the field.

Myasthenia gravis (MG) is the most frequent immune-mediated neurological disorder, characterized by fluctuating muscle weakness. Specific recognition of self-antigens by T-cell receptors (TCRs) and B-cell receptors (BCRs), coupled with T-B cell interactions, activates B cells to produce autoantibodies, which are critical for the initiation and perpetuation of MG. The immune repertoire comprises all functionally diverse T and B cells at a specific time point in an individual, reflecting the essence of immune selectivity. By sequencing the nucleotide sequences of TCRs and BCRs, it is possible to track individual T- and B-cell clones. This review delves into the generation of autoreactive TCRs and BCRs in MG and comprehensively examines the applications of immune repertoire sequencing in understanding disease pathogenesis, developing diagnostic and prognostic markers and informing targeted therapies. We also discuss the current limitations and future potential of this approach.

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.

This Research Highlight discusses a recent publication, where the authors identified an increase in CXCL13 peripheral helper T/follicular helper T cells, which was concomitant with a decrease in CD96 T helper 22 (T22) cells in patients with systemic lupus erythematosus. The genetic and epigenetic cues that reciprocally regulate this pathogenic imbalance of T-cell subsets were also identified, thus providing targets for therapeutic intervention.

Eosinophils have traditionally been viewed as pathological effector cells primarily involved in antiparasitic and allergic immune reactions; however, it is becoming increasingly apparent that eosinophils are multifaceted leukocytes that contribute to a variety of roles in both health and disease. Recent research shows that eosinophils play important immunoregulatory roles across various tissue sites including the gastrointestinal tract, adipose tissue, lung, liver, heart, muscles, thymus and bone marrow. With recent advances in our knowledge and appreciation of eosinophil immunoregulatory functions at these tissue sites, as well as emerging research demonstrating the existence of distinct subsets of eosinophils, a review of this topic is timely. Although some questions remain regarding eosinophil function and heterogeneity, this review summarizes the contemporary understanding of the immunoregulatory roles of eosinophils across various tissues and discusses the latest research on eosinophil heterogeneity and subsets.

As the result of many years of training, becoming a Principal Investigator (PI) is an exciting but also stressful and intimidating career transition step. While navigating this transition we quickly find out that the skills we have crafted throughout our scientific training do not necessarily cover those required to successfully run a research group. Although there is not a common path to ensure success for all new PIs, many of us encounter similar hurdles. The aim of this article is to reflect on my recent experience and mistakes 2 years after initiating this transition, in the hope of highlighting some key aspects that may be beneficial for future new PIs.

Sea urchins are basal deuterostomes that share key molecular components of innate immunity with vertebrates. They are a powerful model for the study of innate immune system evolution and function, especially during early development. Here we characterize the morphology and associated molecular markers of larval immune cell types in a newly developed model sea urchin, Lytechinus pictus. We then challenge larvae through infection with an established pathogenic Vibrio and characterize phenotypic and molecular responses. We contrast these to the previously described immune responses of the purple sea urchin Strongylocentrotus purpuratus. The results revealed shared cellular morphologies and homologs of known pigment cell immunocyte markers (PKS, srcr142) but a striking absence of subsets of perforin-like macpf genes in blastocoelar cell immunocytes. We also identified novel patterning of cells expressing a scavenger receptor cysteine rich (SRCR) gene in the coelomic pouches of the larva (the embryonic stem cell niche). The SRCR signal becomes further enriched in both pouches in response to bacterial infection. Collectively, these results provide a foundation for the study of immune responses in L. pictus. The characterization of the larval immune system of this rapidly developing and genetically enabled sea urchin species will facilitate more sophisticated studies of innate immunity and the crosstalk between the immune system and development.

Challenges don't last; embracing them is crucial to growth and success. Knowing and absorbing this is very important for students in any program and at any level in the academic world. I have my bachelor's and master's degrees from Ladoke Akintola University of Technology and University of Ibadan, Nigeria, respectively. Currently, I am a doctorate student at the Department of Immunology, University of Sao Paulo, Brazil. This article discusses my adaptation to a new environment, overcoming challenges, and the importance of support systems.

Peritoneal adhesion (PA) refers to the abnormal adhesion of the peritoneum either with the peritoneum itself or with tissues and organs that is caused by abdominopelvic surgery, abdominal infection or peritoneal inflammation. PA is associated with various clinical complications, such as abdominal pain and distension, intestinal obstruction, gastrointestinal disorders and female infertility, and adversely affects the quality of life of patients. Macrophages are essential for PA formation and can undergo polarization into classically activated macrophages (M1) and alternatively activated macrophages (M2), which are influenced by the peritoneal microenvironment. By releasing proinflammatory cytokines and reactive oxygen species, M1 macrophages promote peritoneal inflammatory reactions and the resultant formation of adhesion. In contrast, M2 macrophages secrete anti-inflammatory cytokines and growth factors to inhibit PA formation and to promote repair and healing of peritoneal tissues, and thereby play a significant anti-inflammatory role. This review comprehensively explores the function and mechanism of macrophages and their subtypes in PA formation to gain insight into the prevention and treatment of PA based on the modulation of macrophages.

This Special Feature explores the fascinating field of Computational Immunology and features reviews on recent immunology research that used computational tools and concepts to understand the nexus of cancer immunology, autoimmunity and host-pathogen interactions.

The interdisciplinary nature of immunology can make studying not only engaging but also challenging, as understanding immunologic processes and immune system components requires foundational knowledge from several science disciplines. The University of Alabama at Birmingham has a unique, 4-year, Undergraduate Immunology Program (UIP) that provides a comprehensive curriculum in immunology that includes five core courses starting in the second year, at which point, students are in the process of completing basic science sequences. For this study, students in courses across the UIP curriculum were asked to identify basic science topics that relate to four immunology concepts. In addition, students were surveyed on their confidence in understanding each of the basic science topics and were asked to identify the course in which they felt that they had fully learned the topic. Data from this study did not demonstrate a change in students' interdisciplinary science competency from the second to fourth year. Importantly, students reported that they fully understood 11 out of 12 basic science concepts in courses offered in their first and second years, with confidence in basic science topics significantly improving from the second to third year. The lack of demonstrated improvement in interdisciplinary understanding across the curriculum may be attributed to the fact that students are able to integrate basic science topics with foundational immunologic concepts as early as their second year. Importantly, these findings suggest that the integration or review of basic science topics in an immunology course may improve students' comprehension of foundational immunology concepts and interdisciplinary science competency.