Seminars in Immunopathology最新文献

The brain-gut axis constitutes the basis for the bidirectional communication between the central nervous system and the gastrointestinal tract driven by neural, hormonal, metabolic, immunological, and microbial signals. Alterations in the gut microbiome composition as observed in inflammatory bowel diseases can modulate brain function and emerging empirical evidence has indicated that interactions among the brain-gut microbiome-axis seem to play a significant role in the pathogenesis of both inflammatory bowel diseases and psychiatric disorders and their comorbidity. Yet, the immunological and molecular mechanisms underlying the co-occurrence of inflammatory bowel diseases and psychological symptoms are still poorly understood. The aim of this narrative review is to highlight contemporary empirical findings supporting a pivotal role of the gut microbiome in the pathophysiology of highly prevalent neuropsychiatric symptoms in inflammatory bowel diseases such as fatigue, depression, and anxiety. Finally, we focus on microbiome modulation as potential treatment option for comorbid neuropsychiatric symptoms in immune-mediated diseases and especially in inflammatory bowel diseases. High-quality clinical trials are required to clarify how microbiome modulation through dietary interventions or probiotic, prebiotic or synbiotic treatment can be used clinically to improve mental health and thus quality of life of patients with inflammatory bowel diseases.

Metabolic flexibility is key for the function of myeloid cells. Arginine metabolism is integral to the regulation of myeloid cell responses. Nitric oxide (NO) production from arginine is vital for the antimicrobial and pro-inflammatory responses. Conversely, the arginase 1 (ARG1)-dependent switch between the branch of NO production and polyamine synthesis downregulates inflammation and promotes recovery of tissue homeostasis. Creatine metabolism is key for energy supply and proline metabolism is required for collagen synthesis. Myeloid ARG1 also regulates extracellular arginine availability and T cell responses in parasitic diseases and cancer. Cancer, surgery, sepsis and persistent inflammation in chronic inflammatory diseases, such as neuroinflammatory diseases or arthritis, are associated with dysregulation of arginine metabolism in myeloid cells. Here, we review current knowledge on arginine metabolism in different myeloid cell types, such as macrophages, neutrophils, microglia, osteoclasts, tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs) and myeloid-derived suppressor cells (MDSCs). A deeper understanding of the function of arginine metabolism in myeloid cells will improve our knowledge on the pathology of several diseases and may set the platform for novel therapeutic applications.

Overweight and obesity (OWO) are linked to dyslipidemia and low-grade chronic inflammation, which is fueled by lipotoxicity and oxidative stress. In the context of pregnancy, maternal OWO has long been known to negatively impact on pregnancy outcomes and maternal health, as well as to imprint a higher risk for diseases in offspring later in life. Emerging research suggests that individual lipid metabolites, which collectively form the lipidome, may play a causal role in the pathogenesis of OWO-related diseases. This can be applied to the onset of pregnancy complications such as gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP), which in fact occur more frequently in women affected by OWO. In this review, we summarize current knowledge on maternal lipid metabolites in pregnancy and highlight associations between the maternal lipidome and the risk to develop GDM, HDP and childhood OWO. Emerging data underpin that dysregulations in maternal triglyceride, phospholipid and polyunsaturated fatty acid (PUFA) metabolism may play a role in modulating the risk for adverse pregnancy outcomes and childhood OWO, but it is yet premature to convert currently available insights into clinical guidelines. Well-designed large-scale lipidomic studies, combined with translational approaches including animal models of obesity, will likely facilitate the recognition of underling pathways of OWO-related pregnancy complications and child's health outcomes, based on which clinical guidelines and recommendations can be updated.

The intestinal epithelium is a rapidly self-renewing tissue; the rapid turnover prevents the invasion of pathogens and harmful components from the intestinal lumen, preventing inflammation and infectious diseases. Intestinal epithelial barrier function depends on the epithelial cell proliferation and junctions, as well as the state of the immune system in the lamina propria. Polyamines, particularly putrescine, spermidine, and spermine, are essential for many cell functions and play a crucial role in mammalian cellular homeostasis, such as that of cell growth, proliferation, differentiation, and maintenance, through multiple biological processes, including translation, transcription, and autophagy. Although the vital role of polyamines in normal intestinal epithelial cell growth and barrier function has been known since the 1980s, recent studies have provided new insights into this topic at the molecular level, such as eukaryotic initiation factor-5A hypusination and autophagy, with rapid advances in polyamine biology in normal cells using biological technologies. This review summarizes recent advances in our understanding of the role of polyamines in regulating normal, non-cancerous, intestinal epithelial barrier function, with a particular focus on intestinal epithelial renewal, cell junctions, and immune cell differentiation in the lamina propria.

Microchimerism is defined as the presence of a small population of genetically distinct cells within a host that is derived from another individual. Throughout pregnancy, maternal and fetal cells are known to traffic across the feto-maternal interface and result in maternal and fetal microchimerism, respectively. However, the routes of cell transfer, the molecular signaling as well as the timing in which trafficking takes place are still not completely understood. Recently, the presence of inflammation at the feto-maternal interface has been linked with maternal microchimeric cells modulating organ development in the fetus. Here, we review the current literature and suggest that inflammatory processes at the feto-maternal interface tissues are a physiological prerequisite for the establishment of microchimerism. We further propose a spatio-temporal corridor of microchimeric cell migration to potentially explain some biological effects of microchimerism. Additionally, we elaborate on the possible consequences of a shift in this spatio-temporal corridor, potentially responsible for the development of pathologies in the neonate.

The management of autoimmune diseases is currently limited by therapies that largely suppress the immune system, often resulting in partial and temporary remissions. Cellular immunotherapies offer a targeted approach by redirecting immune cells to correct the underlying autoimmunity. This review explores the latest advances in cellular immunotherapies for autoimmune diseases, focusing on various strategies, such as the use of chimeric antigen receptor (CAR) T cells, chimeric auto-antibody receptor (CAAR) T cells, regulatory T cells (Tregs), and tolerogenic dendritic cells (TolDCs). We review recent preclinical studies and results from clinical trials that demonstrate the potential for these therapies to either deplete autoreactive cells or promote immune tolerance through broad or selective targeting of immune cell populations. Key challenges such as ensuring specificity, preventing off-target effects, and improving the longevity of therapeutic effects are discussed. The evolving landscape of cellular immunotherapies holds promise for more durable treatment responses and increased specificity for autoimmune disease treatment.

Despite advances in medicine and antimicrobial research, viral infections continue to pose a major threat to human health. While major strides have been made in generating vaccines and small molecules to combat emerging pathogens, new modalities of treatment are warranted in diseases where there is a lack of treatment options, or where treatment cannot fully eradicate pathogens, as in HIV infection. Cellular therapies, some of which are FDA approved for treating cancer, take advantage of our developing understanding of the immune system, and harness this knowledge to enhance, or direct, immune responses toward infectious agents. As with cancer, viruses that evade immunity, do so by avoiding immune recognition or by redirecting the cellular responses that would eradicate them. As such, infusing virus specific immune cells has the potential to improve patient outcomes and should be investigated as a potential tool in the arsenal to fight infection. The present manuscript summarizes key findings made using cellular therapies for the treatment of viral infections, focusing on the potential that these strategies might have in controlling disease.

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.