Immunology & Cell Biology最新文献

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.

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.

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.

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.

Understanding antigen-specific T-cell responses is crucial for advancing immunotherapies and vaccine development. This study proposes a novel approach combining two complementary assays: the 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay (tracking proliferation over 0-48 h) and the VPD450 dye dilution assay (tracking proliferation over 4-6 days). Integrating these techniques provides additional insights into T-cell proliferation kinetics. Both assays were independently optimized using anti-CD3 and anti-CD28 polyclonal T cell stimulation. 1 μM VPD450 is suitable for assessing T-cell proliferation. The EdU concentration should match the stimulation strength, requiring higher concentrations to efficiently track DNA replication detection during increased cellular division. Day 5 was the optimal read-out day for the EdU incorporation assay. We then combined the VPD450 dye dilution and EdU incorporation assays. As a proof of principle, we stimulated PBMCs from healthy donors with tetanus toxoid to assess antigen-specific T-cell responses. Additionally, we demonstrated the assay's application in drug research by evaluating proliferation in a mixed lymphocyte reaction with abatacept, an agonistic anti-CTLA-4 antibody. This combined approach offers qualitative insights into T-cell proliferation kinetics, beneficial for assessing novel vaccine efficiency or for designing new treatments targeting T cell proliferation, such as in autoimmune settings.

Neurodegeneration and neuroinflammation disorders are mainly the result of the deposition of various proteins, such as α-synuclein, amyloid-β and prions, which lead to the initiation and activation of inflammatory responses. Different chemokines are involved in the infiltration and movement of inflammatory leukocytes into the central nervous system (CNS) that express chemokine receptors. Dysregulation of several members of chemokines has been shown in the CNS, cerebrospinal fluid and peripheral blood of patients who have neurodegenerative disorders. Upon infiltration of various cells, they produce many inflammatory mediators such as cytokines. Besides them, some CNS-resident cells, such as neurons and astrocytes, are also involved in the pathogenesis of neurodegeneration by producing chemokines. In this review, we summarize the role of chemokines and their related receptors in the pathogenesis of neurodegeneration and neuroinflammation disorders, including multiple sclerosis, Parkinson's disease and Alzheimer's disease. Therapeutic strategies targeting chemokines or their related receptors are also discussed in this article.

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.

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.