Immunology & Cell Biology最新文献

In this Research Highlight, we discuss two recently published studies that show that germinal center B cells undergoing multiple rounds of cell division strongly suppress their rate of somatic hypermutation. These studies provide an explanation for how high-affinity germinal center B cells avoid deleterious mutations that could impair antibody affinity maturation.

Scientific public engagement activities and participation in bioscience discussions need to be open to everyone, as they play a significant role in connecting the general public to research and breaking down barriers of scientific skepticism. In a society increasingly shaped by scientific progress, it is crucial that everyone, regardless of their background or ability, feels empowered to participate in these conversations. However, this is not usually the case for blind or low-vision communities who are often excluded, in part due to scientific outreach events being historically limited to visual imagery. To break down such barriers, we organized a multisensory exhibition as part of the Cambridge Festival 2024. The initiative was inspired by Monash Sensory Science, a targeted outreach program designed to engage individuals who are blind, have low vision or diverse needs. Our aim was to use novel, tactile and informative models to explore the role of the immune system in the central nervous system health and disease, focusing on two inflammation models: traumatic brain injury and multiple sclerosis. In Sensory Science, we fostered the involvement of the blind and low-vision community through tactile scientific posters, resin and plaster brain models, and interactive experiences involving heat, sound, tactile poetry and photography. The Sensory Science exhibition held during March 2024 not only promoted equality but also reminded us that true innovation lies in the collective efforts of a diverse and inclusive community.

Immune cells and blood metabolites play essential roles in the development of polycystic ovary syndrome (PCOS); however, it remains unclear whether blood metabolites mediate the causal relationship between immune cells and PCOS. This study aimed to delineate the causal relationships among immune cells, PCOS and potential blood metabolites through Mendelian randomization (MR). A two-sample MR analysis was conducted using inverse variance weighting as the primary method to determine the causation between immune cells and PCOS risk. This was supplemented by a two-step MR analysis to assess the mediating role of blood metabolites between immune cells and PCOS. In addition, a series of sensitivity analysis methods were employed to test the robustness of the results. We also performed a reverse MR to evaluate the possibility of reverse causal relationships. Our findings identified 22 immune cell phenotypes causally linked to PCOS, with 12 acting as risk factors and 10 as protective factors for PCOS. Furthermore, 45 blood metabolites or ratios were causally related to PCOS. Mediation analysis revealed that X-25519 levels mediated 9.2% of the causal relationship between the absolute count of CD28⁻CD25⁺⁺ CD8^br and PCOS. In addition, N-acetylglucosamine/n-acetylgalactosamine levels and adenosine 5′-monophosphate levels mediated 6.7% and –11.1%, respectively, in the causation between naive DN(CD4⁻ CD8⁻) %T cell and PCOS. The aspartate-to-citrate ratio mediated 8.6% of the causal relationship between CD20⁻ CD38⁻ %B cells and PCOS. Finally, reverse MR studies did not identify any reverse causation between the 22 immune cell phenotypes and PCOS. This study elucidates the causal links between immune cells and PCOS, highlighting the potential roles of four blood metabolites in mediating the interaction between immune cells and PCOS, thus providing new targets for research and therapeutic interventions.

Phagocytosis is a critical immunological process that enables the immune system to recognize and eliminate foreign pathogens and self-derived pathogenic molecules. Improving the overall understanding of this immune mechanism during malarial infection is imperative. The mechanisms by which phagocytosis eradicates malaria parasites, particularly Plasmodium falciparum, remain incompletely understood and warrant further investigation. In this context, previous studies have shown that various factors such as phagocyte cell subclasses, plasma protein molecules and Plasmodium evasion tactics influence the phagocytic process differently. However, the mechanisms underlying phagocytic activity during P. falciparum infections are still ambiguous. In this review, we summarize key immunological aspects and current knowledge of phagocytic activity during P. falciparum infection. We highlight the significant involvement of distinct active cells that induce phagocytosis. Additionally, we discuss the implications of phagocytosis and potential therapeutic approaches to enhance its effectiveness.

In this article for the “Highlights of 2024” series, we discuss antibody–drug conjugates (ADCs), which are an emerging class of targeted cancer therapies that harness the specificity of monoclonal antibodies to deliver cytotoxic agents directly to tumor cells. ADCs bind to tumor-associated antigens, undergo internalization via receptor-mediated endocytosis, and release their cytotoxic payload intracellularly, reducing systemic toxicity. This highly selective mechanism has led to significant advancements in oncology, improving treatment efficacy while minimizing adverse effects.

In this manuscript for the “Highlights of 2024” series, this is me trying to summarize recent discoveries regarding the emerging regulatory and effector roles of γδ T cells during sepsis, both in human patients and in mouse models. The new findings not only aid our understanding of key immunological and pathophysiological pathways that hit differently during the course of the disease but may also have clinical relevance for a life-threatening condition that requires swift intervention and tailored patient management.

Scientists and researchers represent a broad diversity of genders, races, and abilities, emphasising the importance of intersectionality in healthcare and STEMM. However, with diversity come systemic barriers that must be addressed to achieve equity and inclusion. Overcoming these challenges is essential to enrich scientific discovery and drive medical progress. This Special Feature of Immunology & Cell Biology on “Advancing Equity and Inclusion in Healthcare: an immunological call to action” highlights key barriers to the entry and retention of underrepresented minorities in healthcare and STEMM. We also examine the individual, institutional and systemic changes needed to ensure that intersectionality fuels innovation and that solutions are as dynamic and inclusive as the challenges they seek to address.

In this article for the “Highlights of 2024” Series, we discuss natural killer cells, which are essential players in immune defense, with their function tightly regulated by cytokines and ligand–receptor interactions. We discuss important recent findings that have uncovered critical regulatory pathways shaping NK cell activity.

I never imagined my career would take me beyond the laboratory bench. As a postdoctoral researcher at the Hudson Institute of Medical Research, I was deeply invested in understanding the mechanisms behind ovarian cancer progression, driven by curiosity and the hope that my work might one day improve outcomes for patients. But science isn’t just about discovery—it's also about impact. And somewhere along the way, I realized that my passion extended beyond experiments and data—I wanted to help shape the research landscape itself. That realisation led me to my current role as a Research Advisor for the Ovarian Cancer Research Foundation (OCRF), where I now work to bridge the gap between research and funding, ensuring that the needs of those with a lived experience of ovarian cancer align with the research. The transition from academic research to the not-for-profit sector wasn’t without its challenges. I had to navigate uncertainty, redefine my professional identity and learn to recognise the value of my transferable skills—critical thinking, science communication and strategic planning. This journey has reinforced what I haven’t always realized: science isn’t confined to the laboratory. It's in the conversations we have, the policies we influence and the way we shape the future of research. My career continues to evolve, and while I don’t know exactly what the future holds, one thing remains certain: I am committed to making a difference, in whatever form that takes.

Cancer-associated aberrant glycosylation can be detected by the macrophage galactose-type C-type lectin (MGL) receptor; however, whether this interaction enhances or deadens cancer development along with the associated immune response has not been well established. To determine the role of mouse MGL1 in colitis-associated colon cancer (CAC), azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced tumor development was compared between Mgl1 knockout (Mgl1^−/−) mice and their wild-type (WT) littermates. At 75 days post-CAC induction, colon tumor tissue contained more highly glycosylated proteins, representing potential ligands for the mMGL1 receptor, than did healthy colon tissue. The Mgl1^−/− CAC mice scored lower in disease activity indices and had fewer colonic tumors. In addition, the colonic crypt architecture was less damaged, and mucin production was more significant than in the WT CAC mice. Furthermore, Mgl1^−/− CAC mice displayed higher percentages of CD4⁺ and CD8⁺ T cells in the peripheral blood, and colonic lamina propria; and lower percentages of myeloid-derived suppressor cells (MDSCs). Additionally, less macrophage (Mφ) and natural killer (NK) cell infiltration and lower levels of iNOS and arginase were found in the tumor microenvironment of Mgl1^−/− CAC mice compared with WT mice. These results suggest that the mMGL1 receptor may recognize aberrant glycosylation in colon cancer, which may trigger an inflammatory microenvironment and favor colon tumorigenesis.