Immunology and Cell Biology

The field of neuroimmunology is quickly expanding and, as the primary immune cell of the brain, microglia are truly in the spotlight. In 2023, the number of microglia related articles published on PubMed rose to 5152. This number has consistently increased year on year and has more than doubled since 2013, as we begin to appreciate the role of microglia in brain development, health and disease. The year 2023 continued to bring new important discoveries, extending our knowledge of microglia biology. This image was created in BioRender...

In this article for the Highlights of 2023 Series, we discuss four recent articles that investigated thymic B cells, in both mice and humans. These studies provide important novel insights into the biology of this unique B-cell population, from their activation and differentiation to their role in promoting the negative selection of thymocytes and the generation of regulatory T cells.

Unraveling the complexities of T cell aging is essential for developing targeted interventions to enhance immune function in the elderly. This article for the Highlights of 2023 Series integrates recent findings published in 2023, offering a panoramic view of the current understanding of T cell aging and its implications.

The cells presented in this work are not classified as cells that make up the immune system. They, however, present functions and molecules, which are characteristic of immune cells. These characteristic functions are, for example, sensing threat, performing phagocytosis, presentation of foreign antigens, cytokine release or enhancing immune memory. The enlisted immune response mechanisms are carried out by the possession of molecules such as Toll-like receptors, receptors for the Fc fragment of IgG, major histocompatibility complex class II molecules, costimulatory CD80/CD86 proteins and molecules needed for NLRP3 (NOD-like family pyrin domain containing 3) inflammasome activation...

Increased permeability of the intestinal epithelial layer is linked to the pathogenesis and perpetuation of a wide range of intestinal and extra-intestinal diseases. Infecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed as a treatment for many of the same diseases. Helminths induce immunoregulatory changes in their host which could decrease epithelial permeability, which is highlighted as a potential mechanism through which helminths treat disease...

The significance of metabolites in orchestrating immune cells is now recognized to be on par with other key immune modulators, such as cytokines or chemokines. Seminal discoveries have now been built upon with discoveries that have acted to take the discipline to new heights, particularly in T-cell immunity. This accelerated progress has uncovered a plethora of opportunities for pharmacological intervention, with the aim of harnessing immunometabolism for refined immune modulation across several pathologies...

Resident macrophages of various mammalian organs are characterized by several distinctive features in their gene expression profile and phenotype, including involvement in the regulation of organ functions, as well as reduced sensitivity to proinflammatory activation factors. The reasons for the formation of such a specific phenotype remain the subject of intensive research. Some papers emphasize the role of the origin of organ macrophages. Other studies indicate that monocytes that develop in the red bone marrow are also able to form resident macrophages with a phenotype characteristic of a particular organ, but this requires appropriate microenvironmental conditions...

In 2023, several significant discoveries on the function of microRNAs in the immune system were reported. Here we discuss several notable papers that revealed important functions in T cells.

Mentorship refers to the guidance given by a mentor to a less experienced individual to enhance their professional and personal development. For graduate research students, seeking independent mentors external to their institution offers the rewarding opportunity to obtain objective guidance on a variety of work, study and life matters. This article outlines the steps taken to develop a professional society-based, international mentoring program of over 70 participants. This 6-month program aimed to connect graduate research students with more senior academic scientists in response to the limited networking opportunities imposed by the coronavirus disease 2019 (COVID-19) pandemic in Australia...

Epigenetic modifications, particularly through methylation of DNA packaging histones, play a pivotal role in controlling gene expression. Aberrant patterns of histone methylation have been associated with the development and progression of hematological malignancies. Unraveling the impact of aberrant histone marks on gene expression and leukemogenesis has spurred a concerted effort to develop clinically effective epigenetic therapies. In malignancies associated with the accumulation of histone H3 lysine trimethylation (H3K27me3), one such intervention involves preventing the deposition of this repressive histone mark by inhibiting the histone-modifying enzymes EZH1 and EZH2...

Staphylococcus aureus is a significant bacterial pathogen in both community and hospital settings, and the escalation of antimicrobial-resistant strains is of immense global concern. Vaccination is an inviting long-term strategy to curb staphylococcal disease, but identification of an effective vaccine has proved to be challenging. Three well-characterized, ubiquitous, secreted immune evasion factors from the staphylococcal superantigen-like (SSL) protein family were selected for the development of a vaccine...

Age-associated B cells (ABCs) are a stable subset of memory B lymphocytes that develop during microbial infections and in autoimmune diseases. Despite growing appreciation of their phenotypic and functional characteristics, the transcriptional networks involved in ABC fate commitment and maintenance have remained elusive. In their recent publication, Dai et al. tackle this problem, leveraging both mouse models and human diseases to reveal zinc finger E-box-binding homeobox 2 (ZEB2) as a key transcriptional regulator of ABC lineage specification...

Immunologists are very social people-they love to meet other immunologists and talk about immunology (and immunologists). Constantly! γδ T-cell researchers are no exception. On the contrary, as there are not so many of them compared to, say, researchers working on dendritic cells, they especially crave frequent interactions with like-minded scientists. This is where the technological solutions being developed during the coronavirus disease 2019 (COVID-19) pandemic come into play that have, almost overnight, allowed researchers to hold meetings and lectures online...

Science communication is often confined to spoken, written or graphical form, neglecting the integration of other tools that would open inclusive scientific dialog to the low-vision community. To address this barrier, members from the Monash Rheumatology clinical and laboratory research groups formed a Lupus Sensory Science team to create a breakout room at the 2023 Monash Sensory Science Exhibit on Autoimmunity. Our goal was to develop multimodal displays and artworks to engage participants with blindness and low vision with the immunological underpinnings of systemic lupus erythematosus (SLE)...

To educate members of the blind, low-vision and diverse needs communities on the pathogenesis of the chronic autoimmune disease, type 1 diabetes, members of our team with research expertise in immune-mediated diseases, participated in the 2023 Monash Sensory Science (MSS) Exhibition. Using QR code linked audio commentary, participants were guided through tactile displays demonstrating normal insulin action in the regulation of blood glucose levels and its vital role in providing energy to tissues, followed by displays describing the various stages of the immune system's aberrant attack and the eventual complete destruction of the insulin producing beta-cells of the pancreatic islets in type 1 diabetes...

Fibroblastic reticular cells (FRCs) construct microanatomical niches that support lymph node (LN) homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here, we investigated the role of the transcription factor SpiB that is expressed in LN FRCs. Conditional ablation of SpiB in FRCs impaired the FRC network in the T-cell zone of LNs, leading to reduced numbers of FRCs and altered homeostatic functions including reduced CCL21 and interleukin-7 expression...

Natural killer (NK) cells are cytotoxic lymphocytes important for viral defense. West Nile virus (WNV) infection of the central nervous system (CNS) causes marked recruitment of bone marrow (BM)-derived monocytes, T cells and NK cells, resulting in severe neuroinflammation and brain damage. Despite substantial numbers of NK cells in the CNS, their function and phenotype remain largely unexplored. Here, we demonstrate that NK cells mature from the BM to the brain, upregulate inhibitory receptors and show reduced cytokine production and degranulation, likely due to the increased expression of the inhibitory NK cell molecule, MHC-I...

Monash Sensory Science is a scientific outreach initiative specifically tailored to members of the community who are blind, have low vision and have diverse needs. The purpose of this initiative is to showcase Australian science and encourage greater participation in science from these often-overlooked communities. This article presents our experience in establishing Monash Sensory Science at Monash University and inspiring other institutions to launch similar outreach events.

We explored the frequency of CD14- CD10- CD45+ HLA-DR- SSC++ neutrophils (CD10- neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10- neutrophils in the peripheral blood from HC and patients with NHL was detected...

CD4+ forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) are essential in maintaining immune tolerance and suppressing excessive immune responses. Tregs also contribute to tissue repair processes distinct from their roles in immune suppression. For these reasons, Tregs are candidates for targeted therapies for inflammatory and autoimmune diseases, and in diseases where tissue damage occurs. MT-2 cells, an immortalized Treg-like cell line, offer a model to study Treg biology and their therapeutic potential. In the present study, we use clustered regularly interspaced palindromic repeats (CRISPR)-mediated knockdown of FOXP3 in MT-2 cells to understand the transcriptional and functional changes that occur when FOXP3 is lost and to compare MT-2 cells with primary human Tregs...