Seminars in Immunopathology最新文献

{"title":"Macrophage clock of pregnancy: circadian and metabolic control of decidual macrophage.","authors":"Dongyong Yang, Kristin Thiele, Tailang Yin, Lianghui Diao","doi":"10.1007/s00281-025-01057-6","DOIUrl":"https://doi.org/10.1007/s00281-025-01057-6","url":null,"abstract":"<p><p>The temporal regulation of immune responses during pregnancy is crucial for successful gestation. Yet, the specific mechanisms controlling macrophage function across gestational stages remain poorly understood. Here, we introduce the concept of the \"macrophage clock of pregnancy\", describing how molecular clock and cellular metabolism coordinate macrophage function across gestational stages. The molecular mechanisms underlying circadian control of macrophage function are examined, as well as hormones secreted by the pineal gland and their relevance to pregnancy-related processes. These pathways orchestrate key macrophage functions in pregnancy: modifying the uterine epithelium during implantation, supporting spiral artery remodeling, maintaining fetal tolerance, and initiating labor. Recent evidence shows that environmental factors such as shift work and extension of artificial light exposure can disturb macrophage function. The temporal regulation of macrophages also depends on metabolic signals, with distinct patterns of glycolysis, oxidative phosphorylation, and fatty acid metabolism corresponding to different gestational phases. Disruption of these temporal and metabolic signals - whether through circadian misalignment or metabolic dysfunction - correlates with pregnancy complications including recurrent pregnancy loss, preeclampsia, and preterm birth. We propose that monitoring macrophage temporal dynamics could provide early indicators of pregnancy complications, while targeting clock-controlled pathways may offer new therapeutic strategies. Understanding the temporal aspects of macrophage function opens new approaches for treating pregnancy disorders through precise immunological timing.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"30"},"PeriodicalIF":7.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660109","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":"Immunopathological insights into endometriosis: from research advances to future treatments.","authors":"Yangyang Dai, Zi Ye, Xiang Lin, Songying Zhang","doi":"10.1007/s00281-025-01058-5","DOIUrl":"10.1007/s00281-025-01058-5","url":null,"abstract":"<p><p>Endometriosis is a chronic gynecological disease and a major global concern for women's health. With advancing knowledge of the condition, the classic definition of endometriosis as \"endometrium-like tissue outside the uterus\" now appears insufficient to explain its pathophysiology, as it overlooks the complex involvement of multiple systems in disease development. Immunological changes have been recognized in endometriosis for decades, and growing evidence substantiates that immunopathological alterations are a hallmark of the disease. Imbalanced immune cell populations and cellular dysfunctions within both the innate and adaptive immune systems, along with aberrant inflammatory cytokines, contribute to the inflammation associated with endometriosis. Moreover, immune cell dysfunctions such as reduced natural killer (NK) cell activity, impaired dendritic cell (DC) maturation and inhibited T cell function via immune checkpoints (ICPs) make the microenvironment also immune-suppressive, facilitating the immune evasion of endometriotic lesions. Endometriosis associated inflammation also sabotages female fertility across multiple stages, including ovarian function, fertilization, embryo development and pregnancy complications. Recognition of the inflammatory and immune-suppressive microenvironment associated with endometriosis leads to the discovery of potential immunotherapeutic targets. Established treatments like non-steroid anti-inflammatory drugs (NSAIDs) and hormone therapies harbor immunomodulatory properties. Other immune-based therapies such as immune cell therapies, cytokine-targeting therapies and immune checkpoint inhibitors (ICIs), which have demonstrated significant efficacy in many chronic inflammatory diseases including cancers, may hold substantial promise as future treatments for endometriosis.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"31"},"PeriodicalIF":7.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660108","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":"Impact of endocrine disrupting chemicals on macrophages at the maternal-fetal interface.","authors":"Bin Zhao, Qinsheng Lu, Miaojuan Chen, Gendie E Lash","doi":"10.1007/s00281-025-01055-8","DOIUrl":"https://doi.org/10.1007/s00281-025-01055-8","url":null,"abstract":"<p><p>Pregnancy is a complex and dynamic process, immune homeostasis at the maternal-fetal interface is one of the keys to a successful pregnancy and essential for fetal nutrient exchange and the establishment of immune tolerance. Healthy pregnant women with normally functioning immune systems can successfully maintain a semi-allogeneic fetus to full term without immune-mediated rejection, many immune cells including macrophages, NK cells, T cells, B cells and dendritic cells are involved in this process. In particular, macrophages play a vital role in the establishment of immune tolerance, infection prevention, spiral artery remodeling, and overall maternal and fetal health, due to their plasticity and diversity. However, environmental toxins like endocrine-disrupting chemicals (EDCs) can impact macrophage function, leading to pregnancy-related conditions. This review explores the current knowledge of macrophages at the maternal-fetal interface, their roles in pregnancy, and how EDCs affect their polarization and function.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"29"},"PeriodicalIF":7.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643361","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":"Therapeutic mechanisms of exclusive enteral nutrition in Crohn's disease.","authors":"Krammel Tina, Nie Jiatong, Häcker Deborah, Schwerd Tobias, Aguanno Doriane, Haller Dirk","doi":"10.1007/s00281-025-01053-w","DOIUrl":"10.1007/s00281-025-01053-w","url":null,"abstract":"<p><p>Crohn's disease (CD) is a chronic, relapsing multifactorial inflammatory condition of the gastrointestinal tract, which is diagnosed under the age of 17 in 25% of patients, categorized as pediatric CD (pCD). Exclusive enteral nutrition (EEN) is a first-line therapy for inducing remission in pCD, yet its precise mechanisms remain poorly understood. This review summarizes the complex interplay of EEN-induced protective changes in the gut microbiota, epithelial barrier function and mucosal immune responses. EEN reshapes the gut microbiome by excluding potential pathobionts from the gut mucus layer and increasing protective bacterial and dietary metabolites. Emerging evidence highlights the role of EEN in modulating mitochondrial function, tryptophan metabolism and other metabolites in the intestinal epithelium and immune cells, which may contribute to its therapeutic efficacy. However, high variability in microbiome responses across clinical cohorts and discrepancies between clinical trials and animal models warrant further research to identify functional consequences and therapeutic mechanisms of EEN.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"47 1","pages":"28"},"PeriodicalIF":7.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554373","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":"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":"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":"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}