Seminars in Immunopathology最新文献

The formation and differentiation of mature, motile male germ cells, which can fertilize the egg and ensure successful implantation and development of a healthy embryo, are essential functions of the testis and epididymis. Spermatogenesis is a complex, multistep process that results in the formation of motile haploid gametes, requiring an immunoregulatory environment to maintain tolerance to developing neo-antigens. Different cell types (Sertoli cells, macrophages), immunoregulatory factors and tolerance mechanisms are involved. In this context, possible effects of galectins on the immunoregulatory functions and fertilization ability of male germ cells are postulated. Galectins are pleiotropic lectins involved in the homeostasis, modulation of immune responses and pathological processes. Despite the well-recognized role of galectins in female reproduction, the functions of galectins in the male reproductive organs, particularly the testis and epididymis, remain largely unexplored. Among the galectins, galectin-1 and galectin-3 are the best-studied in these organs. This review summarizes the current knowledge of the cellular expression and the roles of galectin-1 and galectin-3 in testis and epididymis and discusses their functions in spermatogenesis, steroidogenesis, epididymal maturation of spermatozoa and inflammatory response.

Toleration of a semi-allogeneic fetus in the mother's uterus as well as tolerance after allogeneic hematopoietic stem cell transplantation (HSCT) appear to share some immunologic concepts. The existence of microchimeric cells, and the original idea of a bidirectional cell trafficking between mother and child during pregnancy have been known for decades. Today, origins and mechanisms of persistence of microchimeric cells are intensively being elucidated. Both, the translation of the phenomenon of feto-maternal immune tolerance to donor choice or prevention of graft-versus-host disease (GvHD) in HSCT, and the implications of microchimeric cells in and for HSCT are highly intriguing. Yet, differences in detection methods of microchimeric cells, as well as in transplantation protocols impede the comparison of larger cohorts, and limit potential clinical advice. Still, matching of non-inherited maternal antigens (NIMA), which are expressed on maternal microchimeric cells, demonstrated a strong association with decreased risk for the development of acute GvHD in the context of various transplantation strategies. Despite the fact that advances in graft manipulation and immunosuppression ameliorated the safety and outcome after HSCT, NIMA-matching retained a beneficial role in selection of sibling, child, or maternal donors, as well as for cord blood units. Recent findings indicate the existence of a microchimeric stem cell niche, in which only one dominant microchimeric cell population of only one semi-allogeneic origin persists at a time. This implies that studies regarding the impact of (maternal and fetal) microchimerism (MC) on clinical outcome of HSCT should combine analysis of NIMA and direct detection of microchimeric cells from donor and recipient on the verge of HSCT to be efficiently conclusive.

Intrauterine adhesions (IUA), also known as Asherman's syndrome, arise from damage to the basal layer of the endometrium, frequently caused by intrauterine interventions. This damage leads to nonregenerative healing of endometrium resulting in replacement by fibrous connective tissue, which bring about the adherence of opposing endometrium to render the uterine cavity and/or cervical canal partially or completely obliterated. IUA is a common cause of the refractory uterine infertility. Hysteroscopy is the gold standard for diagnosis of IUA. However, the method of accurately predicting the likelihood of achieving a live birth in the future remains established. Classical treatments have shown limited success, particularly in severe cases. Therefore, utilizing new research methods to deepen the understanding of the pathogenesis of IUA will facilitate the new treatment approaches to be found. In this article we briefly described the advances in the pathogenesis of IUA, with focus on inflammation and parenchymal cellular homeostasis disruption, defects in autophagy and the role of ferroptosis, and we also outlined the progress in IUA therapy.

In the intestinal tract, where numerous intestinal bacteria reside, intestinal epithelial cells produce and release various antimicrobial molecules that form a complex barrier on the mucosal surface. These barrier molecules can be classified into two groups based on their functions: those that exhibit bactericidal activity through chemical reactions, such as antimicrobial peptides, and those that physically hinder bacterial invasion, like mucins, which lack bactericidal properties. In the small intestine, where Paneth cells specialize in producing antimicrobial peptides, the chemical barrier molecules primarily inhibit bacterial growth. In contrast, in the large intestine, where Paneth cells are absent, allowing bacterial growth, the primary defense mechanism is the physical barrier, mainly composed of mucus, which controls bacterial movement and prevents their invasion of intestinal tissues. The expression of these barrier molecules is regulated by metabolites produced by bacteria in the intestinal lumen and cytokines produced by immune cells in the lamina propria. This regulation establishes a defense mechanism that adapts to changes in the intestinal environment, such as alterations in gut microbial composition and the presence of pathogenic bacterial infections. Consequently, when the integrity of the gut mucosal barrier is compromised, commensal bacteria and pathogenic microorganisms from outside the body can invade intestinal tissues, leading to conditions such as intestinal inflammation, as observed in cases of inflammatory bowel disease.

To prevent infection, the experience of the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic has led to recognition of the importance of not only vaccines but also the strengthening of mucosal barriers by secretory immunoglobulin A (IgA). Strong mucosal barrier provided by IgA is also possible to prevent allergies and chronic inflammatory conditions in the intestinal tract, since it can protect foreign enemies or antigens at the first line of defense before their invasion. Therefore, it is important to understand the role of IgA antibodies secreted by the mucosa of the body. In this section, we discuss the role of mucosal IgA antibodies in relation to three disease states: control of intestinal microbiota, protection against infection, and allergy. In addition, we provide the evidence in which the quality as well as the quantity of IgA is critical for disease prevention. Therefore, we discuss about novel strategies to enhance mucosal barriers by induction of high-quality IgA.

Ovarian cancer remains a formidable challenge in oncology due to its late-stage diagnosis and limited treatment options. Recent research has revealed the intricate interplay between glycan diversity and the immune microenvironment within ovarian tumors, shedding new light on potential therapeutic strategies. This review seeks to investigate the complex role of glycans in ovarian cancer and their impact on the immune response. Glycans, complex sugar molecules decorating cell surfaces and secreted proteins, have emerged as key regulators of immune surveillance in ovarian cancer. Aberrant glycosylation patterns can promote immune evasion by shielding tumor cells from immune recognition, enabling disease progression. Conversely, certain glycan structures can modulate the immune response, leading to either antitumor immunity or immune tolerance. Understanding the intricate relationship between glycan diversity and immune interactions in ovarian cancer holds promise for the development of innovative therapeutic approaches. Immunotherapies that target glycan-mediated immune evasion, such as glycan-based vaccines or checkpoint inhibitors, are under investigation. Additionally, glycan profiling may serve as a diagnostic tool for patient stratification and treatment selection. This review underscores the emerging importance of glycan diversity in ovarian cancer, emphasizing the potential for unraveling immune interplay and advancing tailored therapeutic prospects for this devastating disease.

Over the last few decades, scientists have recognized the critical role that various components of the extracellular matrix (ECM) play in maintaining homeostatic immunity. Besides, dysregulation in the synthesis or degradation levels of these components directly impacts the mechanisms of immune response during tissue injury caused by tumor processes or the regeneration of the tissue itself in the event of damage. ECM is a complex network of protein compounds, proteoglycans and glycosaminoglycans (GAGs). Hyaluronic acid (HA) is one of the major GAGs of this network, whose metabolism is strictly physiologically regulated and quickly altered in injury processes, affecting the behavior of different cells, from stem cells to differentiated immune cells. In this revision we discuss how the native or chemically modified HA interacts with its specific receptors and modulates intra and intercellular communication of immune cells, focusing on cancer and tissue regeneration conditions.

The first 1000 days of life is a critical period of development in which adverse circumstances can have long-term consequences for the child's health. Maternal immune activation is associated with increased risk of neurodevelopmental disorders in the child. Aberrant immune responses have been reported in individuals with neurodevelopmental disorders. Moreover, lasting effects of maternal immune activation on the offspring's immune system have been reported. Taken together, this indicates that the effect of maternal immune activation is not limited to the central nervous system. Here, we explore the impact of maternal immune activation on the immune system of the offspring. We first describe the development of the immune system and provide an overview of reported alterations in the cytokine profiles, immune cell profiles, immune cell function, and immune induction in pre-clinical models. Additionally, we highlight recent research on the impact of maternal COVID-19 exposure on the neonatal immune system and the potential health consequences for the child. Our review shows that maternal immune activation alters the offspring's immune system under certain conditions, but the reported effects are conflicting and inconsistent. In general, epigenetic modifications are considered the mechanism for fetal programming. The available data was insufficient to identify specific pathways that may contribute to immune programming. As a consequence of the COVID-19 pandemic, more research now focuses on the possible health effects of maternal immune activation on the offspring. Future research addressing the offspring's immune response to maternal immune activation can elucidate specific pathways that contribute to fetal immune programming and the long-term health effects for the offspring.

Skin scar formation following Bacille Calmette-Guérin (BCG) or smallpox (Vaccinia) vaccination is an established marker of successful vaccination and 'vaccine take'. Potent pathogen-specific (tuberculosis; smallpox) and pathogen-agnostic (protection from diseases unrelated to the intentionally targeted pathogen) effects of BCG and smallpox vaccines hold significant translational potential. Yet despite their use for centuries, how scar formation occurs and how local skin-based events relate to systemic effects that allow these two vaccines to deliver powerful health promoting effects has not yet been determined. We review here what is known about the events occurring in the skin and place this knowledge in the context of the overall impact of these two vaccines on human health with a particular focus on maternal-child health.

Biomedical research has witnessed significant strides in manufacturing chimeric antigen receptor T cell (CAR-T) therapies, marking a transformative era in cellular immunotherapy. Nevertheless, existing manufacturing methods for autologous cell therapies still pose several challenges related to cost, immune cell source, safety risks, and scalability. These challenges have motivated recent efforts to optimize process development and manufacturing for cell therapies using automated closed-system bioreactors and models created using artificial intelligence. Simultaneously, non-viral gene transfer methods like mRNA, CRISPR genome editing, and transposons are being applied to engineer T cells and other immune cells like macrophages and natural killer cells. Alternative sources of primary immune cells and stem cells are being developed to generate universal, allogeneic therapies, signaling a shift away from the current autologous paradigm. These multifaceted innovations in manufacturing underscore a collective effort to propel this therapeutic approach toward broader clinical adoption and improved patient outcomes in the evolving landscape of cancer treatment. Here, we review current CAR immune cell manufacturing strategies and highlight recent advancements in cell therapy scale-up, automation, process development, and engineering.