Immunology & Cell Biology最新文献

Sayan Ghosh¹, Sreetama Choudhury¹, Sudeshna Mukherjee¹, Payal Gupta¹, Olivia Chowdhury¹, Rathindranath Baral² & Sreya Chattopadhyay^1,3

1 Department of Physiology, University of Calcutta, UCSTA, Kolkata, India

2 Chittaranjan National Cancer Institute, Kolkata, India

3 Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India

Immunology & Cell Biology 2019; 97: 470–484. https://doi.org/10.1111/imcb.12227

Correction to: Immunology & Cell Biology 2025; https://doi.org/10.1111/imcb.70056

The immunohistochemistry data of thymic tissue from mice in the LPS group panels of Figure 2b and Figure 5b had similar/overlapping architecture, which is not correct and can be noted as a human error. The authors have now added new LPS panels (replicates from same experiment) for Figure 2b and Figure 5b for the readers. The authors confirm that all the experimental results and corresponding conclusions mentioned in the paper remain unaffected. The corrected LPS panels of Figure 2b and Figure 5b are shown as follows:

The authors apologize for this error.

Optic neuritis (ON), characterized by inflammation and demyelination of the optic nerve, is a leading cause of vision impairment. It frequently manifests as the initial symptom and a recurrent syndrome in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). While the diagnosis of ON is relatively straightforward, predicting relapses and managing the disease remain significant challenges. The myelination of retinal ganglion cell axons is essential for the efficient and accurate transmission of signals between optic neurons. Oligodendrocytes, specialized glial cells responsible for myelination, engage in metabolic interactions with neurons. Demyelination and inflammation of the optic nerve locally release a variety of metabolites and inflammatory factors within this unique anatomical region. Cerebrospinal fluid (CSF), in close proximity to ON lesions, is a critical source for identifying metabolic and inflammatory biomarkers that are essential for tracking disease activity and guiding therapeutic decisions. This comprehensive review examines the structure, myelination and demyelination of the optic nerve, as well as the immunopathological mechanisms underlying ON. It also explores changes in CSF constituents, including pleocytosis, antibodies, cytokines, proteins, metabolites and extracellular vesicles. Special emphasis is placed on elucidating the pathological contributions of metabolites in MOGAD, MS and NMOSD. By advancing our understanding of these mechanisms, this review elucidates the potential predictive roles of CSF constituents in acute attacks and relapses of optic neuritis.

Vγ9/Vδ2 T cells represent the largest γδ T-cell population in human blood and possess a unique responsiveness towards microbial organisms by sensing the metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) in the context of the butyrophilin family members BTN2A1 and BTN3A1. Curiously, the bacterium Staphylococcus aureus does not produce HMB-PP but appears to be capable of inducing activation, cytokine expression and proliferation of Vγ9/Vδ2 T cells regardless, through a largely unknown mechanism. We here provide a comprehensive review of the existing literature around Vγ9/Vδ2 T-cell responses to S. aureus and discuss potential pathways, ligands and biological functions.

Activated PI3K delta syndrome 1 (APDS1) is caused by a heterozygous germline gain-of-function (GOF) variant in PIK3CD, which encodes the p110δ catalytic subunit of phosphoinositide 3-kinase (PI3K). APDS1 patients display a broad range of clinical manifestations and perturbations in cellular phenotype. One of the most striking features is the dysregulation of the T-cell compartment, characterized by an increase in memory T cells, including Tfh cells, and a concomitant decrease in naïve T cells. We have previously shown that many of these changes in T-cell populations were T-cell extrinsic and were also induced in WT T cells that developed in the presence of PI3K GOF cells. Here we dissected the drivers of dysregulated T-cell activation using a mouse model of APDS1. This revealed that PI3K GOF macrophages and DCs made little contribution to the aberrant T-cell activation. Instead, PI3K GOF T cells were able to drive the loss of WT naïve CD4⁺ T cells, while dysregulated PI3K GOF B cells mediated an increase in Tfh cells. Surprisingly, despite previous reports of increased PI3K signalling driving dysregulated inflammatory Tregs, we saw no evidence for Pik3cd GOF Tregs acquiring an inflammatory phenotype and driving T-cell activation. These studies provide new insights into the role of PI3K in immune cells and how increased PI3K can drive T- and B-cell dysregulation and contribute to the phenotype of APDS1 patients.

Early career researchers (ECRs) are often faced with uncertainty about their professional futures, a challenge exacerbated by the increasing pressures within the academic research landscape. As ECRs navigate their next steps in science, mentorship is crucial, particularly as they face points of decision-making and possible career diversions from the traditional postdoctoral-to-professor pathway. In response to these challenges, the second iteration of the Australian and New Zealand Society of Immunology (ASI) Mentor-Mentee Program aimed to provide mentorship and training to ECRs about academic career pathways in research and education to bridge the professional communities, values and advice of these two often independent career choices. As a component of the program, three eminent Australian immunologists in research-intensive, teaching and research (TnR) and education-focused careers shared their professional journeys and experiences which led to their chosen career pathways in national workshops. Here, we share their insights, lessons learned and professional development tips to establish an academic career. By outlining the three primary scientific academic career pathways available post-PhD, we aim to inform and inspire the next generation of immunologists as they consider the diversity of possible academic careers ahead.

This study assessed how the interaction between human monocyte dectin-1 and β-glucan induces CD83 expression using THP-1 cells as a model. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to assess the dynamics of membrane-bound CD83 (mCD83) and soluble CD83 (sCD83) expression. Insoluble β-glucan induced CD83 expression more effectively than that of soluble β-glucan. Additionally, our findings indicate that the activation of nuclear factor-kappa B (NFκB) and nuclear factor of activated T cells (NFAT) plays a crucial role in the dectin-1 signaling pathway. sCD83 production is driven by metalloproteinases following mCD83 expression and inhibits mCD83 expression. This study offers novel insights into the immunoregulatory role of CD83 and its regulatory mechanisms, highlighting potential strategies for treating fungal infections and autoimmune diseases.

Immunology & Cell Biology 2025; 103: 820; https://doi.org/10.1111/imcb.70055

Correction to: Immunology & Cell Biology 2025; 103: 192−212. https://doi.org/10.1111/imcb.12848

We made an error in providing the grant number in the acknowledgement section. The current reference to the grant, “This work was supported by the NIH Office of the Director award R01-AI 146581 to Jayajit Das” should be changed to “This work was supported by the NIH Office of the Director award R01-AI143740 to Jayajit Das.”

We apologize for this error.

Multiple sclerosis is a complex neurological disorder, involving both the adaptive and innate immune systems as well as the CNS. The interaction between these systems is complex, and as such, there is the potential for MS therapies to have conflicting effects in different tissues. It is therefore critical that in addition to tissue-specific studies, system-wide effects of potential therapeutic pathways are explored. The circulating protein Gas6 is a promising therapy to promote remyelination in people with multiple sclerosis. Gas6 is a ligand for the TAM family of receptor protein tyrosine kinases that are widely expressed in the immune system and in the CNS, highlighting the potential for multi-system effects as a result of Gas6 treatment. In this study, we demonstrate that global genetic deletion of either Gas6 or the Gas6 receptor Tyro3 results in reduced disease severity following induction of experimental immune encephalomyelitis in mice. The reduction in severity was accompanied by increased expression of both IL-4 and IL-17A in Tyro3 KO mice lymph node tissue and decreased expression of both cytokines in spinal cord tissues. IL-4 is a cytokine known to be protective in inflammatory demyelination in mice. Conversely, the cytokine IL-17A is known to be pathological. The overall shift to reduced disease severity highlights the multi-faceted role of TAM receptor signaling in inflammatory demyelination.

T follicular helper (T_FH) cells are a helper T-cell subset that is defined by their localisation to B-cell areas of secondary lymphoid tissues, enabling them to provide their B-cell helper function. Precursors of T_FH cells migrate to the B-cell follicles by upregulating CXCR5 and downregulating CCR7, a process that can be blocked by S1PR1 overexpression. T_FH cells and their precursors also express the early activation antigen CD69, which is a negative regulator of S1PR1. In this study, we tested the hypothesis that CD69 expression by T_FH cells is important for their differentiation and localisation after immunization. Genetic deletion of CD69 on T_FH cells and a proportion of their precursors did not alter their formation, nor their ability to support high-affinity B-cell responses. This demonstrates that although CD69 is expressed highly on T_FH cells, it is not necessary for their formation or their B-cell helper functions in lymph nodes (LNs).

Tumor rejection is primarily mediated by cytotoxic T cells, making them critical targets for therapeutic cancer vaccines. Vaccine adjuvants can modulate innate immunity, influencing adaptive immune responses. For particulate adjuvants, such as polymeric nanoparticles, physicochemical properties—including size, charge, composition and antigen location within the formulation—can shape these responses. Free-soluble antigens typically fail to induce sufficient dendritic cell maturation and cross-presentation needed for robust CD8⁺ T-cell activation. However, this can be enhanced by delivering antigen with nanoparticles of appropriate size. While adjuvants like oil-in-water emulsions do not require antigen association for vaccine efficacy, the importance of antigen location in the adjuvanticity of polymeric nanoparticles is less clear. We demonstrate that colocalization of antigen and polymeric nanoparticles through antigen adsorption enhances proliferation and activation of antigen-specific CD8⁺ T cells following intramuscular vaccination. While type 1 conventional dendritic cells (cDC1) can prime CD8⁺ T cells in other settings, their requirement with polymeric nanoparticles has not been fully addressed. We show that nanoparticle-induced CD8⁺ T-cell responses rely on cDC1s. The therapeutic efficacy of a polymeric nanoparticle vaccine was significantly enhanced when antigen was adsorbed on nanoparticles, leading to reduced tumor growth and prolonged survival in mice challenged with immunologically hot (MC38) and cold (B16F10) tumors expressing ovalbumin. Furthermore, vaccination with nanoparticle-adsorbed antigen synergized with anti-PD-1 checkpoint blockade, enhancing protection, especially against B16F10-ovalbumin tumors. This work highlights the role of antigen association with polymeric nanoparticles in eliciting CD8⁺ T-cell responses for the development of effective therapeutic cancer vaccines.