Seminars in Immunopathology最新文献

{"title":"Chimerism and immunological tolerance in solid organ transplantation.","authors":"Birte Ohm, Anastasios D Giannou, David Harriman, Jun Oh, Wolfgang Jungraithmayr, Dimitra E Zazara","doi":"10.1007/s00281-025-01052-x","DOIUrl":"10.1007/s00281-025-01052-x","url":null,"abstract":"<p><p>In solid organ transplantation, chimerism inevitably occurs via the coexistence of donor-derived cells from the graft and host cells throughout the recipient. However, long-term immunosuppressive treatment is needed to suppress host immune responses to the foreign organ graft. The deliberate induction of stable mixed bone marrow chimerism to achieve donor-specific immunological tolerance in solid organ graft recipients is an ambitious goal that may significantly contribute to the long-term survival of solid organ grafts and their recipients. While this strategy has been effectively established in laboratory animals and some promising clinical case series have been reported, widespread clinical application is still limited by the toxicity of the necessary conditioning regimens. On the other hand, the naturally occurring chimeric state resulting from the bidirectional transplacental cell trafficking during pregnancy, the so-called feto-maternal microchimerism, can also induce immune tolerance and thus influence the outcome of mother-to-child or child-to-mother organ transplantation. This review provides an overview of the field's historical development, clinical results, and underlying principles of (micro) chimerism-based tolerance.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"27"},"PeriodicalIF":7.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint for pregnancy.","authors":"Xiaohui Hu, Siying Lai, Aihua Liao","doi":"10.1007/s00281-025-01051-y","DOIUrl":"https://doi.org/10.1007/s00281-025-01051-y","url":null,"abstract":"<p><p>A successful pregnancy relies on the precise regulation of the maternal immune system to recognize and tolerate the allogeneic fetus, while simultaneously preventing infection. Immune checkpoint molecules (ICMs), such as programmed death receptor 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T cell immunoglobulin, and mucin-domain containing-3 (Tim-3), play critical roles in regulating the immune response during pregnancy. Emerging research highlights the therapeutic potential of targeting these molecules to restore the immune balance in complicated pregnancies. Understanding the dynamic regulation of ICMs during pregnancy may provide new insights into the pathogenesis of these conditions and offer novel approaches for clinical interventions. Here, we review the expression patterns and functions of key ICMs at the maternal-fetal interface, and their involvement in maintaining immune tolerance throughout gestation. Additionally, we describe the current understanding of immune checkpoint pathways in the pathogenesis of complicated pregnancies and discuss the potential for therapeutic targeting of these pathways in this setting.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"26"},"PeriodicalIF":7.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mothers and mosquitoes: climate change contributes to the spread of vector-borne pathogens posing a substantial threat to pregnant women.","authors":"Pauline Wiemers, Isabel Graf, Marylyn M Addo, Petra C Arck, Anke Diemert","doi":"10.1007/s00281-025-01050-z","DOIUrl":"https://doi.org/10.1007/s00281-025-01050-z","url":null,"abstract":"<p><p>Infectious diseases have threatened individuals and societies since the dawn of humanity. Certain population groups, including pregnant women, young children and the elderly, are particularly vulnerable to severe infections. Over the past few centuries, advances in medical standards and the availability of vaccines have reduced infection-related mortality and morbidity rates in industrialized countries. However, the global rise in temperatures and increased precipitation present a new challenge, facilitating the broader distribution of disease vectors, such as mosquitoes, bugs and ticks, to higher altitudes and latitudes. Consequently, epidemic and pandemic outbreaks associated with these vectors, such as Zika, West Nile, dengue, yellow fever, chikungunya and malaria, are increasingly impacting diverse populations. This review comprehensively examines how infections associated with climate change disproportionately affect the health and well-being of pregnant women and their unborn children. There has been a noticeable emergence of vector-borne diseases in Europe. Consequently, we stress the importance of implementing measures that effectively protect pregnant women from these increasing infections globally and regionally. We advocate for initiatives to safeguard pregnant women from these emerging threats, beginning with enhanced education to raise awareness about the evolving risks this particularly vulnerable population faces.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"25"},"PeriodicalIF":7.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The sweet and the bitter sides of galectin-1 in immunity: its role in immune cell functions, apoptosis, and immunotherapies for cancer with a focus on T cells.","authors":"Julianna Novák, Tamás Takács, Álmos Tilajka, Loretta László, Orsolya Oravecz, Emese Farkas, Nándor Gábor Than, László Buday, Andrea Balogh, Virág Vas","doi":"10.1007/s00281-025-01047-8","DOIUrl":"10.1007/s00281-025-01047-8","url":null,"abstract":"<p><p>Galectin-1 (Gal-1), a member of the β-galactoside-binding soluble lectin family, is a double-edged sword in immunity. On one hand, it plays a crucial role in regulating diverse immune cell functions, including the apoptosis of activated T cells. These processes are key in resolving inflammation and preventing autoimmune diseases. On the other hand, Gal-1 has significant implications in cancer, where tumor cells and the tumor microenvironment (TME) (e.g., tumor-associated fibroblasts, myeloid-derived suppressor cells) secrete Gal-1 to evade immune surveillance and promote cancer cell growth. Within the TME, Gal-1 enhances the differentiation of tolerogenic dendritic cells, induces the apoptosis of effector T cells, and enhances the proliferation of regulatory T cells, collectively facilitating tumor immune escape. Therefore, targeting Gal-1 holds the potential to boost anti-tumor immunity and improve the efficacy of cancer immunotherapy. This review provides insights into the intricate role of Gal-1 in immune cell regulation, with an emphasis on T cells, and elucidates how tumors exploit Gal-1 for immune evasion and growth. Furthermore, we discuss the potential of Gal-1 as a therapeutic target to augment current immunotherapies across various cancer types.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"24"},"PeriodicalIF":7.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota-dependent modulation of intestinal anti-inflammatory CD4⁺ T cell responses.","authors":"Madeline Edwards, Leonie Brockmann","doi":"10.1007/s00281-025-01049-6","DOIUrl":"10.1007/s00281-025-01049-6","url":null,"abstract":"<p><p>Barrier organs such as the gastrointestinal tract, lungs, and skin are colonized by diverse microbial strains, including bacteria, viruses, and fungi. These microorganisms, collectively known as the commensal microbiota, play critical roles in maintaining health by defending against pathogens, metabolizing nutrients, and providing essential metabolites. In the gut, commensal-derived antigens are frequently sensed by the intestinal immune system. Maintaining tolerance toward these beneficial microbial species is crucial, as failure to do so can lead to chronic inflammatory conditions like inflammatory bowel disease (IBD) and can even affect systemic immune or metabolic health. The immune system carefully regulates responses to commensals through various mechanisms, including the induction of anti-inflammatory CD4⁺ T cell responses. Foxp3⁺ regulatory T cells (Foxp3⁺ Tregs) and Type 1 regulatory T cells (Tr1) play a major role in promoting tolerance, as both cell types can produce the anti-inflammatory cytokine IL-10. In addition to these regulatory T cells, effector T cell subsets, such as Th17 cells, also adopt anti-inflammatory functions within the intestine in response to the microbiota. This process of anti-inflammatory CD4⁺ T cell induction is heavily influenced by the microbiota and their metabolites. Microbial metabolites affect intestinal epithelial cells, promoting the secretion of anti-inflammatory mediators that create a tolerogenic environment. They also modulate intestinal dendritic cells (DCs) and macrophages, inducing a tolerogenic state, and can interact directly with T cells to drive anti-inflammatory CD4⁺ T cell functionality. The disrupted balance of these signals may result in chronic inflammation, with broader implications for systemic health. In this review, we highlight the intricate interplays between commensal microorganisms and the immune system in the gut. We discuss how the microbiota influences the differentiation of commensal-specific anti-inflammatory CD4⁺ T cells, such as Foxp3⁺ Tregs, Tr1 cells, and Th17 cells, and explore the mechanisms through which microbial metabolites modulate these processes. We further discuss the innate signals that prime and commit these cells to an anti-inflammatory fate.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"23"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microchimerism and pregnancy complications with placental dysfunction.","authors":"Daniel Pitz Jacobsen, Heidi E Fjeldstad, Maria B Olsen, Meryam Sugulle, Anne Cathrine Staff","doi":"10.1007/s00281-025-01045-w","DOIUrl":"10.1007/s00281-025-01045-w","url":null,"abstract":"<p><p>Cells cross the placenta during pregnancy, resulting in proliferation of semiallogeneic cells in the mother and fetus decades later. This phenomenon, termed microchimerism, is documented across mammalian species, implying an evolutionary benefit. Still, short- and long-term effects remain uncertain. Here, we review the dynamics of microchimerism of fetal, maternal, and mother of the proband origin in relation to increasing gestational age and pregnancy complications associated with placental dysfunction including preeclampsia, fetal growth restriction, preterm labor, recurrent miscarriage, and diabetes. We use the two-stage model of preeclampsia as a framework. We recently published a series of papers independently linking increased fetal microchimerism to markers of placental dysfunction (stage 1), severe maternal hypertension (stage 2) and poor glucose control. Placental dysfunction may influence the intrinsic properties of fetal stem cells. Mesenchymal and hematopoietic stem cells isolated from cord blood during preeclampsia display reduced proliferative potential in vitro. Moreover, preeclampsia is shown to disrupt paracrine signaling in mesenchymal stem cells of the umbilical cord. Undesired properties in cells transferred to the mother could have profound negative effects on maternal health. Finally, recent studies indicate that microchimerism is involved in inducing maternal-fetal tolerance. Disruption of this process is associated with pregnancy complications. Long term, the persistence of microchimerism is necessary to sustain specific regulatory T cell populations in mice. This likely plays a role in the proband's future pregnancies and long-term maternal and offspring health. Current evidence indicates that advancements in our understanding of microchimerism could be instrumental in promoting reproductive and long-term health.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"21"},"PeriodicalIF":7.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The when, what, and where of naturally-acquired microchimerism.","authors":"J Lee Nelson, Nathalie C Lambert","doi":"10.1007/s00281-024-01029-2","DOIUrl":"10.1007/s00281-024-01029-2","url":null,"abstract":"<p><p>Naturally acquired microchimerism (Mc) is increasingly recognized as an aspect of normal biology. Maternal-fetal bi-directional exchange during pregnancy creates a Mc legacy for the long-term in both individuals. Maternal Mc in her offspring and Mc of fetal origin in women with previous births are best studied. Other sources include from a known or vanished twin, miscarriage or pregnancy termination, older sibling, or previous maternal pregnancy loss. Mc is pleotropic and protean, present in diverse forms, and changing over time as other aspects of biology. Mc acquired from multiple sources, at different lifespan times, and taking on an array of diverse forms, creates a \"forward, reverse, and horizontal inheritance\" Mc landscape. Mc is found in adaptive and innate immune cells, as resident tissue-specific cells in a wide variety of human tissues, and among other forms as extracellular vesicles. HLA molecules function in a myriad of ways as key determinants for health and are of central importance in interactions between genetically disparate individuals. Studies of autoimmune disease have firmly established a primary role of HLA molecules. Studies of iatrogenic chimerism have established benefit of donor-recipient HLA-disparity against recurrent malignancy after transplantation. HLA molecules and HLA-relationships of families are therefore of particular interest in seeking to understand the role(s) of Mc at the interface of auto-immunity and healthy allo-immunity. This review will begin by providing perspective on Mc in biology followed by a primary focus on persistent Mc according to the human lifespan, in healthy individuals and with illustrative examples of autoimmune diseases.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"20"},"PeriodicalIF":7.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NK cells: shielding senescence homeostasis in the decidua during early pregnancy.","authors":"Zi-Meng Zheng, Jia-Wei Shi, Li Wang, Ming-Qing Li","doi":"10.1007/s00281-025-01048-7","DOIUrl":"10.1007/s00281-025-01048-7","url":null,"abstract":"<p><p>Decidualization, the transformation of endometrial stromal cells into specialized decidual cells, is essential for embryo implantation and pregnancy maintenance. This process involves immune cell infiltration, especially decidual natural killer (dNK) cells, which regulate immune responses and support tissue remodeling. Recent findings suggest that cellular senescence during decidualization is not just a byproduct but plays a functional role in enhancing uterine receptivity. However, excessive senescence leads to complications like recurrent pregnancy loss. dNK cells help maintain decidual homeostasis by clearing senescent cells, preventing their harmful accumulation. The balance between dNK activity and decidual stromal cell (DSC) senescence is crucial for successful implantation and pregnancy outcomes. Disruption of this balance may contribute to pathological conditions. This review delves into the pivotal roles of dNK cells in decidual senescence regulation and discusses therapeutic strategies targeting senescence to improve pregnancy outcomes, and new approaches for treating reproductive disorders.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"22"},"PeriodicalIF":7.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota-derived metabolites in inflammatory bowel disease.","authors":"Martina A Guggeis, Danielle Mm Harris, Lina Welz, Philip Rosenstiel, Konrad Aden","doi":"10.1007/s00281-025-01046-9","DOIUrl":"10.1007/s00281-025-01046-9","url":null,"abstract":"<p><p>Understanding the role of the gut microbiota in the pathogenesis of inflammatory bowel diseases (IBD) has been an area of intense research over the past decades. Patients with IBD exhibit alterations in their microbial composition compared to healthy controls. However, studies focusing solely on taxonomic analyses have struggled to deliver replicable findings across cohorts regarding which microbial species drive the distinct patterns in IBD. The focus of research has therefore shifted to studying the functionality of gut microbes, especially by investigating their effector molecules involved in the immunomodulatory functions of the microbiota, namely metabolites. Metabolic profiles are altered in IBD, and several metabolites have been shown to play a causative role in shaping immune functions in animal models. Therefore, understanding the complex communication between the microbiota, metabolites, and the host bears great potential to unlock new biomarkers for diagnosis, disease course and therapy response as well as novel therapeutic options in the treatment of IBD. In this review, we primarily focus on promising classes of metabolites which are thought to exert beneficial effects and are generally decreased in IBD. Though results from human trials are promising, they have not so far provided a large-scale break-through in IBD-therapy improvement. We therefore propose tailored personalized supplementation of microbiota and metabolites based on multi-omics analysis which accounts for the individual microbial and metabolic profiles in IBD patients rather than one-size-fits-all approaches.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"19"},"PeriodicalIF":7.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dyslipidemia and female reproductive failures: perspectives on lipid metabolism and endometrial immune dysregulation.","authors":"Yuan Zhang, Monira Alzahrani, Svetlana Dambaeva, Joanne Kwak-Kim","doi":"10.1007/s00281-025-01043-y","DOIUrl":"10.1007/s00281-025-01043-y","url":null,"abstract":"<p><p>Dyslipidemia is a common metabolic disorder around the world, with a higher incidence in the population of childbearing age and those experiencing infertility. Increasing research has been focused on the impact of dyslipidemia on female reproduction. This article reviews relevant clinical and basic science research on the effects of dyslipidemia on female reproduction, particularly paying attention to immune inflammatory changes in the endometrium. A comprehensive overview of the physiological effects of lipid metabolism on innate and adaptive immunity is provided, specifically examining the relationship between lipid metabolism and endometrial immune homeostasis, as well as the changes observed in women with reproductive failures. Moreover, the alterations in endometrial gene expressions and immune effectors in women with dyslipidemia and reproductive disorders are discussed, offering a new perspective on the reproductive disorders in women with dyslipidemia. Considering the significant involvement of lipid metabolism in human reproduction, gaining a deeper insight into dyslipidemia and female reproduction could have important clinical implications for the diagnosis and management of female reproductive disorders.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"18"},"PeriodicalIF":7.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}