Immunology & Cell Biology最新文献

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.

Effective scientific communication fosters public support and trust in research, establishing a stronger understanding of health and disease. Making STEM education more accessible is crucial for blind, low-vision and diverse-needs (BLVDN) communities, where grasping complex biomedical concepts can be challenging. Such accessibility promotes equal opportunities and encourages innovation through diverse perspectives. This paper examines the Sensory Science Cambridge exhibition, held at the Cambridge Festival in March 2024, aiming to enhance the accessibility of biomedical concepts for BLVDN communities, inspired by Monash Sensory Science in Australia. The exhibition included several tactile exhibits, including one designed to educate on the nature of human papillomavirus (HPV) infections and their link to cervical cancer through a diorama art piece. We were guided by the question: How can tactile and sensory materials convey HPV infection and its progression to cervical cancer? To achieve this, we developed a tactile diorama for independent navigation, featuring braille keys, explanatory panels and verbal descriptions. The diorama was created through collaboration between scientists and artists, and its effectiveness was evaluated through participant feedback and observational studies during the exhibition. The diorama significantly improved the participants’ understanding of HPV and cervical cancer, providing new or building on existing knowledge. The success of this exhibition project provides a model for using tactile and sensory materials in biomedical education. It highlights the potential of sensory science approaches in making STEM education more accessible and underscores the importance of interdisciplinary collaboration in creating accessible, scientifically rigorous communication tools, offering insights for future inclusive science outreach.

Sphingosine-1-phosphate receptor 1 (S1P₁) ligands effectively reduce immunopathological damage in viral pneumonia models. Specifically, S1P₁ ligands inhibit cytokine storm and help preserve lung endothelial barrier integrity. We recently showed that the S1P receptor ligand ozanimod can be safely administered to hospitalized patients with coronavirus disease 2019 (COVID-19) exhibiting severe symptoms of viral pneumonia, with potential clinical benefits. Here, we extend on this study and investigate the impact of ozanimod on key features of the immune response in patients with severe COVID-19. We quantified circulating cytokine levels, peripheral immune cell numbers, proportions and activation status; we also monitored the quality of the humoral response by assessing anti–severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) antibodies. Our findings reveal that patients receiving ozanimod during acute SARS-CoV-2 infection exhibit significantly reduced numbers of circulating monocytes compared with those receiving standard care. Correspondingly, in the ozanimod-treated group, circulating levels of C–C motif ligand 2 (CCL2) were decreased. While treatment with ozanimod negatively impacted the humoral response to COVID-19 in unvaccinated patients, it did not impair the development of a robust anti–SARS-CoV-2 antibody response in vaccinated patients. These findings suggest that ozanimod influences key immune mechanisms during the acute phase of SARS-CoV-2 infection.

Indigenous representation in Australian biomedical science and pharmacy research remains limited due to systemic barriers, historical marginalization and culturally inappropriate educational frameworks. This article outlines a case study of initiatives at the University of Newcastle (UoN) aimed at addressing these inequities. Central to this effort is the establishment of the Indigenous Student Engagement Committee, which promotes Indigenous participation across all academic stages. Working in conjunction with key programs, including culturally embedded pathways such as the Yapug and Miroma Bunbilla programs, undergraduate and postgraduate research fellowships, and culturally inclusive curricula, demonstrate UoN's commitment to fostering a robust pipeline for Indigenous researchers. The UoN's initiatives are grounded in collaboration with local Aboriginal communities, ensuring relevance and cultural safety. Early engagement programs with primary and secondary schools, supported by partnerships with the Wollotuka Institute, create pathways that demystify science and higher education. Hands-on experiences, such as laboratory work placements, enhance accessibility and interest among Indigenous students. At the tertiary level, efforts focus on indigenizing curricula and providing dedicated spaces and mentorship that nurture academic success and cultural connection. The article also highlights challenges, including the rigidity of traditional funding models, the discomfort of non-Indigenous staff in this space, and the need for flexible, inclusive recruitment practices. Recommendations for addressing these barriers include ongoing cultural capability training, mentorship programs and tailored funding constructs that accommodate community commitments. By outlining the UoN's comprehensive, culturally responsive strategies, this case study offers a model for increasing Indigenous engagement in biomedical sciences. It underscores the importance of systemic change, collaboration and sustained investment in creating equitable pathways for Indigenous students and researchers, ultimately contributing to a more inclusive academic and research environment in Australia.

Gender inequities persist in science, with women encountering significant barriers at various career stages, particularly in fields such as Immunology. This article highlights the work of Immunologists for Gender Equity (IgEquity), a trainee-led organization within the ImmunoX Program at the University of California, San Francisco (UCSF), which is committed to addressing these disparities. Through initiatives focused on community building, mentorship, outreach and advocacy, IgEquity seeks to advance gender equity in academia. We emphasize the critical role that trainee-led organizations can play in driving change and underscore the importance of institutional support in creating lasting, systemic progress toward gender equity in the scientific community.

Activation of CD8⁺ T cells enable them to control virus infections and tumors. This process involves the differentiation of naïve CD8⁺ T cells into effector and memory states, driven by specific transcription factors (TFs). Previously, we have shown that Granzyme A (Gzma) induction in activated CD8⁺ T cells depends on Gata3 and the establishment of a permissive chromatin landscape at the Gzma locus. Interestingly, Gzma expression is independent of IL-4 signaling, which typically upregulates Gata3 in CD4⁺ T cells, suggesting an alternative pathway for Gata3 induction. Here we demonstrate that Notch signals during CD8⁺ T cell activation promote Gzma expression. Inhibition of Notch signaling or loss of the Notch transactivator Rbp-j leads to reduced Gzma expression, with transcriptionally repressive chromatin at the Gzma locus. The genome targets of Gata3 differ in effector CD8⁺ T cells activated with IL-4 compared with those activated with Notch signals or isolated after IAV infection. This indicates that the signals received during CD8⁺ T cell activation can alter the chromatin landscape, affecting Gata3 function. Furthermore, Gata3 deficiency results in reduced IAV-specific CD8⁺ T cell responses and decreased Gzma expression, although the Gzma locus maintains a permissive chromatin landscape. These findings suggest that Notch signals received by virus-specific CD8⁺ T cells prepare the chromatin landscape for Gata3 binding to CD8⁺ lineage-specific gene loci, promoting effective CD8⁺ T cell immunity.

Outbreaks of respiratory virus infections and arbovirus infections both pose a substantial threat to global public health. Clinically, both types of infection range from mild to severe and coinfections may occur more commonly than supposed. Our previous experimental coinfection study in mice demonstrated that prior infection with the arbovirus Semliki Forest virus (SFV) negatively impacted immune responses to influenza A virus (IAV). Here, we investigate whether simultaneous coinfection impacts the outcome of immune responses or disease. Simultaneous SFV and IAV infection did not lead to exacerbated or attenuated disease compared with the single virus infection control groups. SFV brain virus titers and brain pathology, including inflammation and immune responses, were comparable in the coinfection and single infection groups. By contrast, there was enhanced IAV replication, but no exacerbated lung pathology in coinfected mice. The magnitude of IAV-specific CD8⁺ T-cell responses in the lungs was lower compared with IAV-only infection. Considered along with our previous study, this study provides evidence that the timing of viral coinfection is pivotal in determining effects on immune responses, pathological changes and disease outcome.

Sjögren's disease (SjD) is a chronic autoimmune disorder characterized by increased circulating self-reactive B cells. While many of these self-reactive B cells emerge from the bone marrow, it is not known whether they are excluded from or enriched in specific developmental stages in the periphery. The aim of this study was to determine the immunophenotype of circulating self-reactive B cells in SjD to inform more precise therapeutic targeting. Five major B cell populations: transitional, mature naïve, switched memory, double negative and plasmablasts were single-cell sorted and cultured to produce IgG. Self-reactive IgG was identified by ELISA, flow cytometry of permeabilized HEK293 cells and HEp-2 indirect immunofluorescence. Immunoglobulin heavy chains were sequenced by Sanger and next-generation sequencing. Compared with healthy donor controls (HCs), SjD patients had higher frequencies of naïve and CD21^low atypical memory B cell subsets, while antigen-experienced B cells expressed more Ki67 and CD86. B cells recognizing intracellular self-antigens were identified in all stages of peripheral B cell development for SjD and HCs, but frequencies of autoreactive B cells were up to 10-fold higher in SjD. Self-reactive transitional B cells expressed higher surface CD38 and lower surface IgM. An increase in self-reactive B cells throughout peripheral development in SjD compared with HCs suggests that counterselection of autoantibody-bearing B cells during central and peripheral tolerance checkpoints are reduced in SjD. Therapeutic strategies focused on depleting B cells based on B cell receptor specificity rather than the developmental stage would be more efficient to target self-reactive B cells in SjD.

In this article, we discuss our experiences and perspectives in forming a workplace Parents Group. We reflect on the need for these networks, what has worked well, and the challenges we’ve experienced. We also provide some practical advice for those with parenting-related career disruptions for addressing this topic in grant applications.

We recently developed a hybrid protein, tentatively named human MIKO-1 (hMIKO-1), based on the amino acid sequences of human S100A8 (hS100A8) and hS100A9. Human THP-1 macrophages (THP-1m), differentiated from THP-1 cells by phorbol 12-myristate 13-acetate, were used to investigate the immune function of hMIKO-1 as a drug for inflammatory diseases. Western blotting was conducted to confirm whether hMIKO-1 binds with β-actin and nuclear factor-kappa B to form complexes in THP-1m. A polymerase chain reaction (PCR) and quantitative PCR were performed to examine changes in the messenger RNA levels of proinflammatory cytokines in THP-1m. Fluorescent immunochemical staining was used to observe the intracellular localization of hMIKO-1 and hS100A8 or hS100A9 in THP-1m. As observed microscopically, the intracellular localization of hMIKO-1 in THP-1m was consistent with that of hS100A8, suggesting the close involvement of hS100A8 in the intracellular behavior of hMIKO-1 in THP-1m. Western blotting revealed that hMIKO-1 formed complexes with intracellular proteins, such as β-actin and nuclear factor-kappa B, to negatively regulate inflammatory signal transduction in THP-1m. Flow cytometry showed that the binding of hMIKO-1 to THP-1m significantly decreased when THP-1m were preliminarily treated with a sialidase (neuraminidases) cocktail. Therefore, the present results strongly suggest that the binding of hMIKO-1 to THP-1m closely involves the sugar chains of the surface proteins of cells. The messenger RNA expression of each proinflammatory cytokine was significantly suppressed in THP-1m preliminarily treated with hMIKO-1 despite a subsequent stimulation with lipopolysaccharide. In conclusion, hMIKO-1 is a functional molecule that significantly inhibits inflammatory signal transduction in THP-1m.