Immunology & Cell Biology最新文献

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.

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.

The Immunology & Cell Biology Publication of the Year Awards have been established for outstanding studies submitted by first authors who are financial members of the Australian & New Zealand Society for Immunology Inc. in the year of the article's publication. Articles vying for these awards can come from any of the journal categories including Original Articles, Outstanding Observations, Perspectives or Short Communications. The Journal undertakes rigorous review to identify the most outstanding original research articles based on scientific excellence. The winner of the Chris and Bhama Parish ICB Publication of the Year Award is awarded an AU$1000 scholarship provided by Wiley and the runner-up is awarded an AU$500 scholarship provided by Miltenyi.

Every year, an outstanding series of papers are submitted for consideration for the prizes and 2023 was no different, with an exceptional standard of science reported in the papers. It is a great pleasure to announce the winners of the awards for 2023 as follows:

The award-winning papers by Drs Kedzierski and von Borstel highlight the outstanding quality of the work published in Immunology & Cell Biology. My very best congratulations are extended to the awardees on their success. I also thank our sponsor Miltenyi for their support of outstanding science and scientists and the journal. It is hoped that the outstanding quality of these awarded publications will also encourage others to consider Immunology & Cell Biology as a key journal for their cutting-edge research.

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.

T-cell-mediated therapeutic strategies are the most potent effectors of cancer immunotherapy. However, an essential barrier to this therapy in solid tumors is disrupting the anti-cancer immune response, cancer-immunity cycle, T-cell priming, trafficking and T-cell cytotoxic capacity. Thus, reinforcing the anti-cancer immune response is needed to improve the effectiveness of T-cell-mediated therapy. Tumor-associated protease ADAM10, endothelial cells (ECs) and cytotoxic CD8⁺ T cells engage in complex communication via adhesion, transmigration and chemotactic mechanisms to facilitate an anti-cancer immune response. The precise impact of ADAM10 on the intricate mechanisms underlying these interactions remains unclear. This paper broadly explores how ADAM10, through different routes, influences the efficacy of T-cell-mediated therapy. ADAM10 cleaves CD8⁺ T-cell-targeting genes and impacts their expression and specificity. In addition, ADAM10 mediates the interactions of adhesion molecules with T cells and influences CD8⁺ T-cell activity and trafficking. Thus, understanding the role of ADAM10 in these events may lead to innovative strategies for advancing T-cell-mediated therapies.

Myasthenia gravis (MG) is the most frequent immune-mediated neurological disorder, characterized by fluctuating muscle weakness. Specific recognition of self-antigens by T-cell receptors (TCRs) and B-cell receptors (BCRs), coupled with T–B cell interactions, activates B cells to produce autoantibodies, which are critical for the initiation and perpetuation of MG. The immune repertoire comprises all functionally diverse T and B cells at a specific time point in an individual, reflecting the essence of immune selectivity. By sequencing the nucleotide sequences of TCRs and BCRs, it is possible to track individual T- and B-cell clones. This review delves into the generation of autoreactive TCRs and BCRs in MG and comprehensively examines the applications of immune repertoire sequencing in understanding disease pathogenesis, developing diagnostic and prognostic markers and informing targeted therapies. We also discuss the current limitations and future potential of this approach.

Chronic wounds significantly burden health care systems worldwide, requiring novel strategies to ease their impact. Many physiological processes underlying wound healing are well studied but the role of mast cells remains controversial. Mast cells are innate immune cells and play an essential role in barrier function by inducing inflammation to defend the host against chemical irritants and infections, among others. Many mast cell–derived mediators have proposed roles in wound healing; however, in vivo evidence using mouse models has produced conflicting results. Recently, studies involving more complex wound models such as infected wounds, diabetic wounds and wounds healing under psychological stress suggest that mast cells play critical roles in these processes. This review briefly summarizes the existing literature regarding mast cells in normal wounds and the potential reasons for the contradictory results. Focus will be placed on examining more recent work emerging in the last 5 years that explores mast cells in more complex systems of wound healing, including infection, psychological stress and diabetes, with a discussion of how these discoveries may inspire future work in the field.

The humoral response is complex and involves multiple cellular populations and signaling pathways. Bacterial and viral infections, as well as immunization regimens, can trigger this type of response, promoting the formation of microanatomical cellular structures called germinal centers (GCs). GCs formed in secondary lymphoid organs support the differentiation of high-affinity plasma cells and memory B cells. There is growing evidence that the quality of the humoral response is influenced by genetic variants. Using 12 genetically divergent mouse strains, we assessed the impact of genetics on GC cellular traits. At steady state, in the spleen, lymph nodes and Peyer's patches, we quantified GC B cells, plasma cells and follicular helper T cells. These traits were also quantified in the spleen of mice following immunization with a foreign antigen, namely, sheep red blood cells, in addition to the number and size of GCs. We observed both strain- and organ-specific variations in cell type abundance, as well as for GC number and size. Moreover, we find that some of these traits are highly heritable. Importantly, the results of this study inform on the impact of genetic diversity in shaping the GC response and identify the traits that are the most impacted by genetic background.

As the result of many years of training, becoming a Principal Investigator (PI) is an exciting but also stressful and intimidating career transition step. While navigating this transition we quickly find out that the skills we have crafted throughout our scientific training do not necessarily cover those required to successfully run a research group. Although there is not a common path to ensure success for all new PIs, many of us encounter similar hurdles. The aim of this article is to reflect on my recent experience and mistakes 2 years after initiating this transition, in the hope of highlighting some key aspects that may be beneficial for future new PIs.

Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges. This study aimed to harness induced pluripotent stem cell (iPSC) technology to provide a consistent and scalable source of NK cells, overcoming the limitations of traditional sources and enhancing the potential for cancer immunotherapy applications. We developed human placental–derived iPSC lines using reprogramming techniques. Subsequently, an optimized two-step differentiation protocol was introduced to generate high-purity NK cells. Initially, iPSCs were differentiated into hematopoietic-like stem cells using spin-free embryoid bodies (EBs). Subsequently, the EBs were transferred to ultra-low attachment plates to induce NK cell differentiation. iPSC-derived NK (iNK) cells expressed common NK cell markers (NKp46, NKp30, NKp44, CD16 and eomesodermin) at both RNA and protein levels. iNK cells demonstrated significant resilience to cryopreservation and exhibited enhanced cytotoxicity. The incorporation of a chimeric antigen receptor (CAR) construct further augmented their cytotoxic potential. This study exemplifies the feasibility of generating iNK cells with high purity and enhanced functional capabilities, their improved resilience to cryopreservation and the potential to have augmented cytotoxicity through CAR expression. Our findings offer a promising pathway for the development of potential cellular immunotherapies, highlighting the critical role of iPSC technology in overcoming challenges associated with traditional NK cell sources.