Pub Date : 2026-01-09DOI: 10.1016/j.coi.2025.102716
Nico De Crem , Wim Alfons Wuyts
Sarcoidosis is a complex and heterogenous disease of which the diagnosis is based on clinical and radiological findings, histopathology showing non-caseating granulomas, and exclusion of other granulomatous diseases. Several tools are well established in the diagnostic pathway, such as pulmonary function tests, broncho-alveolar lavage, endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial and endobronchial biopsies, the serum biomarkers serum angiotensin converting enzyme and soluble interleukin-2 receptor, and imaging, mainly chest computed tomography (CT), 18-fluorodeoxyglucose-positron emission tomography/CT, and brain and cardiac magnetic resonance imaging. However, continuous efforts in the field have been made, and a variety of novel methods are arising. These might be less invasive, can lead to a more secure diagnosis, promote risk stratification, or guide treatment decisions, especially when combined in a stepwise multimodal approach. In this work, we aim to give an overview of the current diagnostic standards in sarcoidosis and discuss the new kids on the block.
{"title":"Emerging diagnostic techniques in sarcoidosis: a path forward","authors":"Nico De Crem , Wim Alfons Wuyts","doi":"10.1016/j.coi.2025.102716","DOIUrl":"10.1016/j.coi.2025.102716","url":null,"abstract":"<div><div>Sarcoidosis is a complex and heterogenous disease of which the diagnosis is based on clinical and radiological findings, histopathology showing non-caseating granulomas, and exclusion of other granulomatous diseases. Several tools are well established in the diagnostic pathway, such as pulmonary function tests, broncho-alveolar lavage, endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial and endobronchial biopsies, the serum biomarkers serum angiotensin converting enzyme and soluble interleukin-2 receptor, and imaging, mainly chest computed tomography (CT), 18-fluorodeoxyglucose-positron emission tomography/CT, and brain and cardiac magnetic resonance imaging. However, continuous efforts in the field have been made, and a variety of novel methods are arising. These might be less invasive, can lead to a more secure diagnosis, promote risk stratification, or guide treatment decisions, especially when combined in a stepwise multimodal approach. In this work, we aim to give an overview of the current diagnostic standards in sarcoidosis and discuss the new kids on the block.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102716"},"PeriodicalIF":5.8,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915494","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}
Pub Date : 2026-01-09DOI: 10.1016/j.coi.2025.102717
Konstantinos N Panagiotopoulos , Athanasios G Tzioufas , Andreas V Goules
We aim to present recent advancements in predictive markers for lymphomagenesis in SjD, concisely organize existing knowledge, and identify corresponding unmet needs and future perspectives. First, we briefly describe the mechanisms of lymphomagenesis in SjD. Followingly, the reasons justifying the importance of early lymphoma diagnosis in SjD are presented. Subsequently, recent advancements regarding lymphoma risk factors in SjD, both in translational and clinical research, are discussed, and how they fit in the preexisting knowledge landscape. Following, the effects of predicting a high risk of lymphoma development on clinical practice, clinical trials, monitoring strategies, as well as the currently known value of preventive treatment are presented. Lastly, we suggest future perspectives and unmet needs. The paradigm is shifting towards time-sensitive reevaluation of traditional risk factors and analysis of novel markers. Characterization of the exact site of occurrence of pathobiological events is increasingly punctual. Isolated biological B cell hyperactivity seems to be a temporally distant harbinger of lymphomagenesis, while clinical manifestations of B cell hyperactivity potentially signal imminent transition to clinically overt lymphoma. Data regarding protective factors and lymphoma prevention strategies are scarce. Deep learning for lymphoma prediction or automated identification of lymphoma risk factors is completely unexplored. Consensus guidelines regarding lymphoma prediction, monitoring, and prevention are lacking. Further advancements are anticipated in the field of predicting, monitoring, treating, and potentially preventing lymphoma in SjD. That is through refinement of study design, employment of deep learning, and, eventually, development of consensus guidelines to guide both research and clinical practice.
{"title":"Markers predicting lymphoma development in Sjögren disease: current status and future perspectives","authors":"Konstantinos N Panagiotopoulos , Athanasios G Tzioufas , Andreas V Goules","doi":"10.1016/j.coi.2025.102717","DOIUrl":"10.1016/j.coi.2025.102717","url":null,"abstract":"<div><div>We aim to present recent advancements in predictive markers for lymphomagenesis in SjD, concisely organize existing knowledge, and identify corresponding unmet needs and future perspectives. First, we briefly describe the mechanisms of lymphomagenesis in SjD. Followingly, the reasons justifying the importance of early lymphoma diagnosis in SjD are presented. Subsequently, recent advancements regarding lymphoma risk factors in SjD, both in translational and clinical research, are discussed, and how they fit in the preexisting knowledge landscape. Following, the effects of predicting a high risk of lymphoma development on clinical practice, clinical trials, monitoring strategies, as well as the currently known value of preventive treatment are presented. Lastly, we suggest future perspectives and unmet needs. The paradigm is shifting towards time-sensitive reevaluation of traditional risk factors and analysis of novel markers. Characterization of the exact site of occurrence of pathobiological events is increasingly punctual. Isolated biological B cell hyperactivity seems to be a temporally distant harbinger of lymphomagenesis, while clinical manifestations of B cell hyperactivity potentially signal imminent transition to clinically overt lymphoma. Data regarding protective factors and lymphoma prevention strategies are scarce. Deep learning for lymphoma prediction or automated identification of lymphoma risk factors is completely unexplored. Consensus guidelines regarding lymphoma prediction, monitoring, and prevention are lacking. Further advancements are anticipated in the field of predicting, monitoring, treating, and potentially preventing lymphoma in SjD. That is through refinement of study design, employment of deep learning, and, eventually, development of consensus guidelines to guide both research and clinical practice.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102717"},"PeriodicalIF":5.8,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915497","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}
Pub Date : 2026-01-09DOI: 10.1016/j.coi.2025.102718
Daan Peeters, Mathieu Vinken , Raf Van Campenhout
Cellular channels consisting of pannexins facilitate signaling between the intracellular and extracellular environment. In this respect, pannexin channel opening serves as a pivotal trigger for both inflammatory processes and cell death. While pannexin channels also contribute to normal physiological functions, their roles in pathological mechanisms have been more extensively studied. Indeed, aberrant pannexin channel activity contributes to the onset and progression of a plethora of diseases. Not surprisingly, pannexin channels have attracted considerable attention as a biomarker and therapeutic target. Marking the 25th anniversary of the discovery of pannexins, the present paper reviews 25 years of pannexin research, exploring the lifecycle of pannexins, their various functional roles, and their involvement in a multitude of diseases affecting different organ systems in the human body.
{"title":"A throwback on 25 years in pannexin research","authors":"Daan Peeters, Mathieu Vinken , Raf Van Campenhout","doi":"10.1016/j.coi.2025.102718","DOIUrl":"10.1016/j.coi.2025.102718","url":null,"abstract":"<div><div>Cellular channels consisting of pannexins facilitate signaling between the intracellular and extracellular environment. In this respect, pannexin channel opening serves as a pivotal trigger for both inflammatory processes and cell death. While pannexin channels also contribute to normal physiological functions, their roles in pathological mechanisms have been more extensively studied. Indeed, aberrant pannexin channel activity contributes to the onset and progression of a plethora of diseases. Not surprisingly, pannexin channels have attracted considerable attention as a biomarker and therapeutic target. Marking the 25th anniversary of the discovery of pannexins, the present paper reviews 25 years of pannexin research, exploring the lifecycle of pannexins, their various functional roles, and their involvement in a multitude of diseases affecting different organ systems in the human body.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102718"},"PeriodicalIF":5.8,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915495","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}
Pub Date : 2025-12-23DOI: 10.1016/j.coi.2025.102712
Loukas Chatzis , Dimitris Anastasios Palamidas , Thomas Dörner
Sjögren’s disease (SjD) is a chronic autoimmune disorder in which sustained B-cell activation drives glandular injury and systemic complications. Epithelial stress and interferon tone amplify B-cell activating factor (BAFF)-dependent survival, skewing selection toward autoreactive clones in both glands and blood. In addition, single-cell B-cell receptor analyses have uncovered interferon-high endotypes with tissue-imprinted oligoclonality and biased isotype and light-chain usage. Within salivary glands, ectopic germinal centers and FcRL4⁺ B cells act as local ‘training sites,’ integrating Tfh/Tph help, CXCL13 cues, and BAFF/APRIL-NF-κB signaling to sustain plasmablast differentiation. Extrafollicular trajectories — double-negative and age-associated B cells — expand in IFN/TLR7 and IL-21 milieus, while regulatory B-cell restraint is diminished. Emerging data also implicate glycolysis and mTORC1-GLUT1 metabolism in sustaining B-cell hyperactivation. Chronic B-cell receptor signaling and clonal evolution provide a bridge to lymphoma risk. In this review, we outline how these converging pathways define molecular endotypes and propose a precision framework linking them to targeted therapy in SjD.
{"title":"Mapping the B-cell axis in Sjögren’s disease: repertoire, microenvironment, and potential routes to precision treatment","authors":"Loukas Chatzis , Dimitris Anastasios Palamidas , Thomas Dörner","doi":"10.1016/j.coi.2025.102712","DOIUrl":"10.1016/j.coi.2025.102712","url":null,"abstract":"<div><div>Sjögren’s disease (SjD) is a chronic autoimmune disorder in which sustained B-cell activation drives glandular injury and systemic complications. Epithelial stress and interferon tone amplify B-cell activating factor (BAFF)-dependent survival, skewing selection toward autoreactive clones in both glands and blood. In addition, single-cell B-cell receptor analyses have uncovered interferon-high endotypes with tissue-imprinted oligoclonality and biased isotype and light-chain usage. Within salivary glands, ectopic germinal centers and FcRL4⁺ B cells act as local ‘training sites,’ integrating Tfh/Tph help, CXCL13 cues, and BAFF/APRIL-NF-κB signaling to sustain plasmablast differentiation. Extrafollicular trajectories — double-negative and age-associated B cells — expand in IFN/TLR7 and IL-21 milieus, while regulatory B-cell restraint is diminished. Emerging data also implicate glycolysis and mTORC1-GLUT1 metabolism in sustaining B-cell hyperactivation. Chronic B-cell receptor signaling and clonal evolution provide a bridge to lymphoma risk. In this review, we outline how these converging pathways define molecular endotypes and propose a precision framework linking them to targeted therapy in SjD.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102712"},"PeriodicalIF":5.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822528","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}
Pub Date : 2025-12-22DOI: 10.1016/j.coi.2025.102713
Francesco Siracusa , Andres Machicote , Samuel Huber , Nicola Gagliani
The intestinal microbiota transforms dietary components into bioactive metabolites that profoundly influence mucosal and systemic immunity. Short-chain fatty acids, secondary bile acids and tryptophan-derived indoles are among the most studied microbial metabolites shaping T, B and innate immune cell functions through a variety of mechanisms, including receptor signaling, epigenetic modification and metabolic reprogramming. Dietary habits strongly affect the composition of the intestinal microbiota and thus, the production and availability of these microbial metabolites, with consequences that range from protective immune regulation to detrimental inflammatory responses. Here, we review recent findings from mouse and human studies, highlighting how the microbiota–immunity axis can be modulated by diets and discuss implications for tissue homeostasis, infection and chronic inflammatory diseases. Understanding this complex interplay may guide the development of ad hoc dietary and microbial interventions to restore tolerance and improve therapeutic outcomes.
{"title":"Diet-derived microbial metabolites as regulators of immune function","authors":"Francesco Siracusa , Andres Machicote , Samuel Huber , Nicola Gagliani","doi":"10.1016/j.coi.2025.102713","DOIUrl":"10.1016/j.coi.2025.102713","url":null,"abstract":"<div><div>The intestinal microbiota transforms dietary components into bioactive metabolites that profoundly influence mucosal and systemic immunity. Short-chain fatty acids, secondary bile acids and tryptophan-derived indoles are among the most studied microbial metabolites shaping T, B and innate immune cell functions through a variety of mechanisms, including receptor signaling, epigenetic modification and metabolic reprogramming. Dietary habits strongly affect the composition of the intestinal microbiota and thus, the production and availability of these microbial metabolites, with consequences that range from protective immune regulation to detrimental inflammatory responses. Here, we review recent findings from mouse and human studies, highlighting how the microbiota–immunity axis can be modulated by diets and discuss implications for tissue homeostasis, infection and chronic inflammatory diseases. Understanding this complex interplay may guide the development of <em>ad hoc</em> dietary and microbial interventions to restore tolerance and improve therapeutic outcomes.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102713"},"PeriodicalIF":5.8,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822507","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}
The complement system is a central component of innate immunity, mediating opsonization, chemotaxis, cytolysis, and shaping adaptive responses. Deficiencies in complement proteins, whether inherited or acquired, predispose to severe infections, particularly with encapsulated bacteria such as Neisseria meningitidis and Streptococcus pneumoniae. Although rare, inherited defects affect different pathways and may also present with autoimmune or renal diseases. Diagnosis relies on functional and quantitative assays, especially in patients with early-onset or recurrent infections. Complement inhibition, introduced with eculizumab and expanded to agents targeting C3, Factor B, or Factor D, has transformed the management of complement-mediated disorders but unmasked novel infectious risks, including meningococcal disease and invasive fungal infections.
This review summarizes clinical and mechanistic aspects of complement deficiencies, infection risks associated with therapeutic blockade, and current diagnostic strategies. It emphasizes the importance of anticipatory care, vaccination, and prophylaxis as new complement-targeted drugs continue to emerge.
{"title":"Complement deficiencies and infections","authors":"Carine El Sissy , Jérémie Rosain , Mathilde Puel , Cécile Gonnin , Véronique Frémeaux-Bacchi","doi":"10.1016/j.coi.2025.102711","DOIUrl":"10.1016/j.coi.2025.102711","url":null,"abstract":"<div><div>The complement system is a central component of innate immunity, mediating opsonization, chemotaxis, cytolysis, and shaping adaptive responses. Deficiencies in complement proteins, whether inherited or acquired, predispose to severe infections, particularly with encapsulated bacteria such as <em>Neisseria meningitidis</em> and <em>Streptococcus pneumoniae</em>. Although rare, inherited defects affect different pathways and may also present with autoimmune or renal diseases. Diagnosis relies on functional and quantitative assays, especially in patients with early-onset or recurrent infections. Complement inhibition, introduced with eculizumab and expanded to agents targeting C3, Factor B, or Factor D, has transformed the management of complement-mediated disorders but unmasked novel infectious risks, including meningococcal disease and invasive fungal infections.</div><div>This review summarizes clinical and mechanistic aspects of complement deficiencies, infection risks associated with therapeutic blockade, and current diagnostic strategies. It emphasizes the importance of anticipatory care, vaccination, and prophylaxis as new complement-targeted drugs continue to emerge.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102711"},"PeriodicalIF":5.8,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786834","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}
Pub Date : 2025-12-16DOI: 10.1016/j.coi.2025.102705
Elizabeth L Frost , Arijita Jash , Angelo D’Alessandro , Krystalyn E Hudson , James C Zimring
Despite multiple alloantigenic differences in every allotransfusion, only 3–6% of transfusion recipients develop a detectable alloantibody even with multiple transfusions. Moreover, patients typically become alloimmunized only to some of the alloantigens to which they are exposed. In recent decades, precursor frequency of antigen-specific T and B cells has been demonstrated to be a key determinant of adaptive immunity. Given the small differences between donor and recipient alloantigens (typically a single amino acid), precursor frequencies for T and B cells are predicted to be extremely low for a given alloantigen. In this review, it is argued based upon existing evidence in the literature and new data presented herein that linked recognition occurs with red blood cell (RBC) alloantigens resulting in a dramatically increased precursor frequency for CD4+ T cell help with no increase in B cell precursor frequency. The hypothesis is forwarded that B cell precursor frequency is a limiting factor in RBC alloimmunization.
{"title":"The role of linked recognition and B cell precursor frequency in alloimmunization to transfused RBCs","authors":"Elizabeth L Frost , Arijita Jash , Angelo D’Alessandro , Krystalyn E Hudson , James C Zimring","doi":"10.1016/j.coi.2025.102705","DOIUrl":"10.1016/j.coi.2025.102705","url":null,"abstract":"<div><div>Despite multiple alloantigenic differences in every allotransfusion, only 3–6% of transfusion recipients develop a detectable alloantibody even with multiple transfusions. Moreover, patients typically become alloimmunized only to some of the alloantigens to which they are exposed. In recent decades, precursor frequency of antigen-specific T and B cells has been demonstrated to be a key determinant of adaptive immunity. Given the small differences between donor and recipient alloantigens (typically a single amino acid), precursor frequencies for T and B cells are predicted to be extremely low for a given alloantigen. In this review, it is argued based upon existing evidence in the literature and new data presented herein that linked recognition occurs with red blood cell (RBC) alloantigens resulting in a dramatically increased precursor frequency for CD4<sup>+</sup> T cell help with no increase in B cell precursor frequency. The hypothesis is forwarded that B cell precursor frequency is a limiting factor in RBC alloimmunization.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102705"},"PeriodicalIF":5.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776942","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}
Pub Date : 2025-12-16DOI: 10.1016/j.coi.2025.102709
Roberta E Ledda, Camilla Roberti, Nicola Sverzellati
Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating epithelioid granulomata, most commonly involving the lungs and thoracic lymph nodes. Although definitive diagnosis relies on tissue biopsy, characteristic findings detected on computed tomography (CT) often allow a confident diagnosis. Atypical imaging patterns, however, can complicate differentiation from other diseases. Different high-resolution CT phenotypes of pulmonary sarcoidosis have been recently defined by the multinational Delphi consensus study, aiming at providing a basis for the development of a formal classification of pulmonary sarcoidosis. Chest CT plays a central role in the diagnosis and follow-up, complemented by magnetic resonance imaging and nuclear imaging, while quantitative approaches have shown promise in enhancing the evaluation of pulmonary sarcoidosis.
This review focuses on the role of imaging in pulmonary sarcoidosis, highlighting both typical and atypical radiological manifestations.
{"title":"From X-rays to advanced imaging modalities in pulmonary sarcoidosis","authors":"Roberta E Ledda, Camilla Roberti, Nicola Sverzellati","doi":"10.1016/j.coi.2025.102709","DOIUrl":"10.1016/j.coi.2025.102709","url":null,"abstract":"<div><div>Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating epithelioid granulomata, most commonly involving the lungs and thoracic lymph nodes. Although definitive diagnosis relies on tissue biopsy, characteristic findings detected on computed tomography (CT) often allow a confident diagnosis. Atypical imaging patterns, however, can complicate differentiation from other diseases. Different high-resolution CT phenotypes of pulmonary sarcoidosis have been recently defined by the multinational Delphi consensus study, aiming at providing a basis for the development of a formal classification of pulmonary sarcoidosis. Chest CT plays a central role in the diagnosis and follow-up, complemented by magnetic resonance imaging and nuclear imaging, while quantitative approaches have shown promise in enhancing the evaluation of pulmonary sarcoidosis.</div><div>This review focuses on the role of imaging in pulmonary sarcoidosis, highlighting both typical and atypical radiological manifestations.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102709"},"PeriodicalIF":5.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776860","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}
Pub Date : 2025-12-16DOI: 10.1016/j.coi.2025.102710
Mehmet Ali Hoskan, Vanessa Sperandio
Indole is an abundant metabolite in the mammalian gut. Both mammals and microorganisms sense it. Indole is a signal used to communicate and gauge the gut environment. Indole is produced by bacteria that encode the tryptophanase enzyme. However, indole sensing is not limited to the organisms that produce it; mammals, as well as microbes incapable of producing this molecule, have receptors for it. Indole signaling has varying activities, from contributing to intestinal barrier integrity, modifying brain signaling, and preventing aging. In microorganisms, it represses biofilm formation and modulates the virulence of enteric pathogens, among other phenotypes. Although there is a renaissance in indole research, comprehensive knowledge of its signaling pathways is limited. Here, we review indole signaling across species and kingdoms. By understanding the integration of the activity of indole at the host, microbiota, and pathogen interface, one may be able to develop novel dietary and therapeutic approaches.
{"title":"Indole sensing in host, microbiota, and pathogen interactions","authors":"Mehmet Ali Hoskan, Vanessa Sperandio","doi":"10.1016/j.coi.2025.102710","DOIUrl":"10.1016/j.coi.2025.102710","url":null,"abstract":"<div><div>Indole is an abundant metabolite in the mammalian gut. Both mammals and microorganisms sense it. Indole is a signal used to communicate and gauge the gut environment. Indole is produced by bacteria that encode the tryptophanase enzyme. However, indole sensing is not limited to the organisms that produce it; mammals, as well as microbes incapable of producing this molecule, have receptors for it. Indole signaling has varying activities, from contributing to intestinal barrier integrity, modifying brain signaling, and preventing aging. In microorganisms, it represses biofilm formation and modulates the virulence of enteric pathogens, among other phenotypes. Although there is a renaissance in indole research, comprehensive knowledge of its signaling pathways is limited. Here, we review indole signaling across species and kingdoms. By understanding the integration of the activity of indole at the host, microbiota, and pathogen interface, one may be able to develop novel dietary and therapeutic approaches.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102710"},"PeriodicalIF":5.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776877","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}
Pub Date : 2025-12-12DOI: 10.1016/j.coi.2025.102708
Meichang Peng , Haitao Sun
The microbiota-gut-brain axis (MGBA) has been recognized as an important communication network between the gut and the brain. This network operates through immune, neural, and endocrine pathways, wherein microbiota-derived metabolites act as essential messengers regulating MGBA. Among gut metabolites, indole and its derivatives derived from tryptophan by gut microbiota are emerging as critical factors along the MGBA. By activating the aryl hydrocarbon receptor (AhR), these metabolites help modulate neuroimmune responses by regulating microglial activation, astrocyte reactivity, and the integrity of the blood-brain barrier (BBB), thereby exerting impacts on neuroinflammation, nerve regeneration, and BBB function. Although animal studies are promising, turning these findings into clinical translation is still difficult due to the conditional effects of AhR signaling, the reliable biomarkers, and the challenges in gut metabolite delivery. This review aims to summarize recent advances in understanding the indole-brain connection, critically evaluate current therapeutic strategies, and highlight the need for more targeted therapies.
{"title":"The indole-brain connection: neuroimmune mechanisms and therapy","authors":"Meichang Peng , Haitao Sun","doi":"10.1016/j.coi.2025.102708","DOIUrl":"10.1016/j.coi.2025.102708","url":null,"abstract":"<div><div>The microbiota-gut-brain axis (MGBA) has been recognized as an important communication network between the gut and the brain. This network operates through immune, neural, and endocrine pathways, wherein microbiota-derived metabolites act as essential messengers regulating MGBA. Among gut metabolites, indole and its derivatives derived from tryptophan by gut microbiota are emerging as critical factors along the MGBA. By activating the aryl hydrocarbon receptor (AhR), these metabolites help modulate neuroimmune responses by regulating microglial activation, astrocyte reactivity, and the integrity of the blood-brain barrier (BBB), thereby exerting impacts on neuroinflammation, nerve regeneration, and BBB function. Although animal studies are promising, turning these findings into clinical translation is still difficult due to the conditional effects of AhR signaling, the reliable biomarkers, and the challenges in gut metabolite delivery. This review aims to summarize recent advances in understanding the indole-brain connection, critically evaluate current therapeutic strategies, and highlight the need for more targeted therapies.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102708"},"PeriodicalIF":5.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733538","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}
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