Pub Date : 2025-12-11DOI: 10.1016/j.coi.2025.102707
Ting Yang , Negaar Goudarzi , Frans G.M Kroese , Xavier Mariette , Sarah Pringle , Gaetane Nocturne
Sjögren’s disease (SjD) is a systemic autoimmune disorder characterized by a striking tropism for epithelial tissues, particularly the salivary and lacrimal glands. Lack of function of the salivary glands (SGs) leads to a panoply of symptoms, dramatically reducing patient quality of life. Over the past decades, research has established that the ductal epithelium is not merely a structural component but rather a central player in the immunopathology of the SG in SjD. The aim of this review is to briefly reassess the evidence supporting the role of SG epithelium in the pathogenesis of the disease and to highlight how the development of new epithelial models of the salivary glands, namely organoids, may pave the way for novel research avenues and personalized therapeutic strategies.
{"title":"Salivary gland organoids and the future of modeling autoimmune epithelitis in Sjögren’s disease","authors":"Ting Yang , Negaar Goudarzi , Frans G.M Kroese , Xavier Mariette , Sarah Pringle , Gaetane Nocturne","doi":"10.1016/j.coi.2025.102707","DOIUrl":"10.1016/j.coi.2025.102707","url":null,"abstract":"<div><div>Sjögren’s disease (SjD) is a systemic autoimmune disorder characterized by a striking tropism for epithelial tissues, particularly the salivary and lacrimal glands. Lack of function of the salivary glands (SGs) leads to a panoply of symptoms, dramatically reducing patient quality of life. Over the past decades, research has established that the ductal epithelium is not merely a structural component but rather a central player in the immunopathology of the SG in SjD. The aim of this review is to briefly reassess the evidence supporting the role of SG epithelium in the pathogenesis of the disease and to highlight how the development of new epithelial models of the salivary glands, namely organoids, may pave the way for novel research avenues and personalized therapeutic strategies.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102707"},"PeriodicalIF":5.8,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733539","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 : 2025-12-09DOI: 10.1016/j.coi.2025.102706
Teng Teng Xu , Camille Guyot , Peter J Murray
Tryptophan (TRP) metabolism has long been associated with cancer immunity, primarily through the kynurenine pathway mediated by indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase (TDO2). Both enzymes can deplete TRP within cells and in local microenvironments, triggering dysfunction of T cells with anti-tumor functions. This view fostered the development of IDO1/TDO2 inhibitors, which ultimately failed in clinical trials. However, we now know that TRP metabolism in tumors is far more complex than anticipated. Recent work highlights the dual, context-dependent roles of TRP-depleting enzymes. Importantly, advances in spatial profiling have uncovered that TRP-metabolizing enzymes are not uniformly expressed but instead form distinct metabolic niches within tumors. These niches shape local TRP availability, metabolite gradients, downstream metabolic signaling, and immune responses in ways that cannot be captured by bulk or single-cell approaches alone. This review synthesizes emerging insights into the diverse and spatially defined functions of TRP metabolism in cancer and discusses how integrating spatial omics may guide next-generation therapeutic strategies beyond IDO1 inhibition.
{"title":"Revisiting tryptophan metabolism in cancer: complexity, context, and spatial heterogeneity","authors":"Teng Teng Xu , Camille Guyot , Peter J Murray","doi":"10.1016/j.coi.2025.102706","DOIUrl":"10.1016/j.coi.2025.102706","url":null,"abstract":"<div><div>Tryptophan (TRP) metabolism has long been associated with cancer immunity, primarily through the kynurenine pathway mediated by indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase (TDO2). Both enzymes can deplete TRP within cells and in local microenvironments, triggering dysfunction of T cells with anti-tumor functions. This view fostered the development of IDO1/TDO2 inhibitors, which ultimately failed in clinical trials. However, we now know that TRP metabolism in tumors is far more complex than anticipated. Recent work highlights the dual, context-dependent roles of TRP-depleting enzymes. Importantly, advances in spatial profiling have uncovered that TRP-metabolizing enzymes are not uniformly expressed but instead form distinct metabolic niches within tumors. These niches shape local TRP availability, metabolite gradients, downstream metabolic signaling, and immune responses in ways that cannot be captured by bulk or single-cell approaches alone. This review synthesizes emerging insights into the diverse and spatially defined functions of TRP metabolism in cancer and discusses how integrating spatial omics may guide next-generation therapeutic strategies beyond IDO1 inhibition.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102706"},"PeriodicalIF":5.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727694","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 : 2025-12-08DOI: 10.1016/j.coi.2025.102704
Patompong Ungprasert , Brandon P Moss
Clinically overt granulomatous involvement of the nervous system, or neurosarcoidosis, occurs in up to 5% of patients with sarcoidosis. Diagnosing neurosarcoidosis is often challenging due to its highly heterogeneous and frequently nonspecific clinical presentations, as well as the difficulty in obtaining tissue confirmation. In practice, the diagnosis of neurosarcoidosis is typically made based on supportive findings from ancillary tests — such as magnetic resonance imaging and cerebrospinal fluid analysis — in conjunction with the exclusion of alternative diagnoses in patients with known extraneural sarcoidosis. Current treatment recommendations are largely based on expert opinion and retrospective studies. Several factors should guide the initial treatment strategy, including disease extent, severity, functional impairment, comorbidities, and patient preferences. Glucocorticoids remain the cornerstone of therapy, with steroid-sparing agents and biologics frequently required in more severe cases.
{"title":"Sarcoidosis of the nervous system: a rare but serious manifestation","authors":"Patompong Ungprasert , Brandon P Moss","doi":"10.1016/j.coi.2025.102704","DOIUrl":"10.1016/j.coi.2025.102704","url":null,"abstract":"<div><div>Clinically overt granulomatous involvement of the nervous system, or neurosarcoidosis, occurs in up to 5% of patients with sarcoidosis. Diagnosing neurosarcoidosis is often challenging due to its highly heterogeneous and frequently nonspecific clinical presentations, as well as the difficulty in obtaining tissue confirmation. In practice, the diagnosis of neurosarcoidosis is typically made based on supportive findings from ancillary tests — such as magnetic resonance imaging and cerebrospinal fluid analysis — in conjunction with the exclusion of alternative diagnoses in patients with known extraneural sarcoidosis. Current treatment recommendations are largely based on expert opinion and retrospective studies. Several factors should guide the initial treatment strategy, including disease extent, severity, functional impairment, comorbidities, and patient preferences. Glucocorticoids remain the cornerstone of therapy, with steroid-sparing agents and biologics frequently required in more severe cases.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102704"},"PeriodicalIF":5.8,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716807","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 : 2025-12-05DOI: 10.1016/j.coi.2025.102703
Sylvia Raftopoulou , Athanasios-Dimitrios Bakasis , Clio P Mavragani
Sjögren’s disease (SjD) is a systemic autoimmune disorder marked by chronic immune activation, with a central role attributed to the interferon (IFN) system. The so-called ‘IFN signature’ at both tissue and peripheral levels has long been recognized as a hallmark of SjD, and recent advances have provided a more detailed molecular understanding of this dysregulation. Nevertheless, the aberrant expression and signaling of type I, II, and, more recently, type III IFNs reflect a complex network of interactions between epithelial and immune cells. This crosstalk is multidirectional, temporospatial, and highly dynamic, shaping the heterogeneity of disease activity, clinical course, and patient phenotypes and endotypes.
Therapeutic targeting of IFN pathways has emerged as a major focus in SjD, with several clinical trials providing valuable insight. While preliminary benefits have been overwhelmingly promising, outcomes remain somewhat variable, influenced by factors such as trial design, patient stratification, disease stage, and underlying immunological endotypes. These challenges underscore the need for refined approaches to harness IFN modulation effectively in clinical practice.
This review summarizes current knowledge of the three IFN families and their contribution to SjD pathogenesis, while highlighting recent research advancements that underscore their promise as therapeutic targets. By integrating clinical and translational perspectives, we aim to clarify our understanding of the role of IFNs in SjD and provide a framework for future research and therapy development approaches.
{"title":"Interferons in Sjogren’s disease: current status and future prospects","authors":"Sylvia Raftopoulou , Athanasios-Dimitrios Bakasis , Clio P Mavragani","doi":"10.1016/j.coi.2025.102703","DOIUrl":"10.1016/j.coi.2025.102703","url":null,"abstract":"<div><div>Sjögren’s disease (SjD) is a systemic autoimmune disorder marked by chronic immune activation, with a central role attributed to the interferon (IFN) system. The so-called ‘IFN signature’ at both tissue and peripheral levels has long been recognized as a hallmark of SjD, and recent advances have provided a more detailed molecular understanding of this dysregulation. Nevertheless, the aberrant expression and signaling of type I, II, and, more recently, type III IFNs reflect a complex network of interactions between epithelial and immune cells. This crosstalk is multidirectional, temporospatial, and highly dynamic, shaping the heterogeneity of disease activity, clinical course, and patient phenotypes and endotypes.</div><div>Therapeutic targeting of IFN pathways has emerged as a major focus in SjD, with several clinical trials providing valuable insight. While preliminary benefits have been overwhelmingly promising, outcomes remain somewhat variable, influenced by factors such as trial design, patient stratification, disease stage, and underlying immunological endotypes. These challenges underscore the need for refined approaches to harness IFN modulation effectively in clinical practice.</div><div>This review summarizes current knowledge of the three IFN families and their contribution to SjD pathogenesis, while highlighting recent research advancements that underscore their promise as therapeutic targets. By integrating clinical and translational perspectives, we aim to clarify our understanding of the role of IFNs in SjD and provide a framework for future research and therapy development approaches.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102703"},"PeriodicalIF":5.8,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681212","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 : 2025-12-03DOI: 10.1016/j.coi.2025.102702
Siba P Raychaudhuri , Smriti K Raychaudhuri
Tissue resident memory T cells (TRM) cells are a recently defined subtype of nonrecirculating memory T cells with longevity and protective functions in peripheral tissues. The discovery of T cells resident in diverse tissues has altered our understanding of adaptive immunity with respect to site-specific immune response. For frontline defense against infections, TRM cells are essential. Accumulating evidence also implies that TRM cells are likely to contribute to the relapse and chronicity in autoimmune diseases, including psoriatic disease. A number of studies have shown the relationship between the pathogenesis of psoriasis and skin-resident memory T cells. Here, we discussed recent insights into the generation, homing, survival, and retention of TRM cells and shared our perspectives on the functions of TRM cells in the recurrence of psoriasis and psoriatic arthritis (PsA). This review summarizes the role of TRM cells in the pathology of psoriasis/PsA, with a view to develop potential novel therapies and therapeutic targets.
组织常驻记忆T细胞（Tissue resident memory T cells， TRM）是最近发现的一种非循环记忆T细胞亚型，在外周组织中具有长寿和保护功能。驻留在不同组织中的T细胞的发现改变了我们对适应性免疫的理解，即位点特异性免疫反应。对于抵抗感染的一线防御，TRM细胞是必不可少的。越来越多的证据也表明，TRM细胞可能导致自身免疫性疾病（包括银屑病）的复发和慢性。许多研究表明银屑病的发病机制与皮肤驻留记忆T细胞有关。在这里，我们讨论了TRM细胞的产生、归巢、存活和保留的最新见解，并分享了我们对TRM细胞在银屑病和银屑病关节炎（PsA）复发中的功能的看法。本文综述了TRM细胞在银屑病/PsA病理中的作用，以期开发潜在的新疗法和治疗靶点。
{"title":"Is psoriatic arthritis a dissemination of cutaneous psoriatic TRM cells? Role of tissue-resident memory T cells (TRM) in psoriatic disease","authors":"Siba P Raychaudhuri , Smriti K Raychaudhuri","doi":"10.1016/j.coi.2025.102702","DOIUrl":"10.1016/j.coi.2025.102702","url":null,"abstract":"<div><div>Tissue resident memory T cells (TRM) cells are a recently defined subtype of nonrecirculating memory T cells with longevity and protective functions in peripheral tissues. The discovery of T cells resident in diverse tissues has altered our understanding of adaptive immunity with respect to site-specific immune response. For frontline defense against infections, TRM cells are essential. Accumulating evidence also implies that TRM cells are likely to contribute to the relapse and chronicity in autoimmune diseases, including psoriatic disease. A number of studies have shown the relationship between the pathogenesis of psoriasis and skin-resident memory T cells. Here, we discussed recent insights into the generation, homing, survival, and retention of TRM cells and shared our perspectives on the functions of TRM cells in the recurrence of psoriasis and psoriatic arthritis (PsA). This review summarizes the role of TRM cells in the pathology of psoriasis/PsA, with a view to develop potential novel therapies and therapeutic targets.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102702"},"PeriodicalIF":5.8,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145672895","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}
Primary central nervous system vasculitis, also known as primary angiitis of CNS (PACNS), is a rare and heterogeneous inflammatory disorder of blood vessels restricted to the central nervous system. The most common presenting symptoms are headache, focal neurological deficits, and altered cognition. Subtypes of PACNS can have different presentations. Diagnosis is challenging due to clinical, imaging, and histopathological heterogeneity, as well as numerous mimics. The goal of diagnostic work-up is to establish that the neurological presentation is due to an underlying vasculitis based on angiographic or histopathologic features and to exclude infection, systemic vasculitis, or other mimics. Treatment is based on anecdotal evidence and consensus, and includes glucocorticoids and cyclophosphamide for induction of remission, as well as mycophenolate mofetil, rituximab, azathioprine, and methotrexate for maintenance therapy. Only two-thirds of the patients achieve a good neurological outcome. A detailed understanding of the etiopathogenesis and heterogeneity will be necessary for developing more effective biomarkers, precision therapies, and improved outcomes.
{"title":"Primary angiitis of the central nervous system","authors":"Sushmitha Meghashyam , Fatema J Serajee , Aviraag V Prakash , Denise Altinok , AHM Mahbubul Huq","doi":"10.1016/j.coi.2025.102691","DOIUrl":"10.1016/j.coi.2025.102691","url":null,"abstract":"<div><div>Primary central nervous system vasculitis, also known as primary angiitis of CNS (PACNS), is a rare and heterogeneous inflammatory disorder of blood vessels restricted to the central nervous system. The most common presenting symptoms are headache, focal neurological deficits, and altered cognition. Subtypes of PACNS can have different presentations. Diagnosis is challenging due to clinical, imaging, and histopathological heterogeneity, as well as numerous mimics. The goal of diagnostic work-up is to establish that the neurological presentation is due to an underlying vasculitis based on angiographic or histopathologic features and to exclude infection, systemic vasculitis, or other mimics. Treatment is based on anecdotal evidence and consensus, and includes glucocorticoids and cyclophosphamide for induction of remission, as well as mycophenolate mofetil, rituximab, azathioprine, and methotrexate for maintenance therapy. Only two-thirds of the patients achieve a good neurological outcome. A detailed understanding of the etiopathogenesis and heterogeneity will be necessary for developing more effective biomarkers, precision therapies, and improved outcomes.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102691"},"PeriodicalIF":5.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569814","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 : 2025-11-11DOI: 10.1016/j.coi.2025.102690
Marcin Radziszewski , Kandice L Tessneer , Christopher J Lessard
Sjögren’s disease (SjD) is the second most common systemic autoimmune disease in the United States. SjD patients are predominantly women 30–50 years of age and exhibit heterogeneous clinical manifestations, including symptoms of extensive dryness, chronic fatigue, and joint pain, and various major organ involvement. Late onset, clinical heterogeneity, and limited mechanistic understanding of its etiology frequently lead to delayed or misdiagnosis. Although the etiology of SjD is unclear, candidate gene studies and population-based genome-wide association studies suggest that SjD results from an interplay between genetics and environment. Defining the genetic susceptibility of SjD remains an important research focus to improve the understanding of SjD etiology and the development of diagnostic and treatment options. Unfortunately, the genetic understanding of SjD lags far behind that of other related autoimmune diseases. This review provides a brief history of key milestones in the field of SjD genetics and highlights several areas of future research that will bolster the discovery power of ongoing genetic studies and define the underlying mechanisms that drive disease etiology.
{"title":"The power of genetics in decoding Sjögren’s disease: current status and future development","authors":"Marcin Radziszewski , Kandice L Tessneer , Christopher J Lessard","doi":"10.1016/j.coi.2025.102690","DOIUrl":"10.1016/j.coi.2025.102690","url":null,"abstract":"<div><div>Sjögren’s disease (SjD) is the second most common systemic autoimmune disease in the United States. SjD patients are predominantly women 30–50 years of age and exhibit heterogeneous clinical manifestations, including symptoms of extensive dryness, chronic fatigue, and joint pain, and various major organ involvement. Late onset, clinical heterogeneity, and limited mechanistic understanding of its etiology frequently lead to delayed or misdiagnosis. Although the etiology of SjD is unclear, candidate gene studies and population-based genome-wide association studies suggest that SjD results from an interplay between genetics and environment. Defining the genetic susceptibility of SjD remains an important research focus to improve the understanding of SjD etiology and the development of diagnostic and treatment options. Unfortunately, the genetic understanding of SjD lags far behind that of other related autoimmune diseases. This review provides a brief history of key milestones in the field of SjD genetics and highlights several areas of future research that will bolster the discovery power of ongoing genetic studies and define the underlying mechanisms that drive disease etiology.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102690"},"PeriodicalIF":5.8,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497970","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}
Recent advancements in microbiome research have revealed the restorative capacities of postbiotics, including indole and its derivatives generated via bacterial tryptophan metabolism. Widespread in prokaryotic and eukaryotic communities, indole and its derivatives are uniquely suited to promote host physiology and homeostasis at the host/microbe interface. In addition to suppressing the bacterial pathogenesis, the antioxidant, anti-inflammatory, antidiabetic, antihypertensive, immunomodulatory, and metabolic activities of indole and its derivatives make these postbiotics an attractive therapeutic option. However, their clinical translation is impeded by pharmacokinetic constraints, structural promiscuity, and formulation difficulties. This review examines the current status of indole bioactivities, identifies translational challenges, and suggests the use of artificial intelligence as a method for establishing a comprehensive framework for future translational development.
{"title":"Toward indole postbiotics precision therapy via AI-powered drug delivery technologies","authors":"Puccetti Matteo , Pariano Marilena , Wojtylo Paulina Anna , Ricci Maurizio , Stefano Giovagnoli","doi":"10.1016/j.coi.2025.102692","DOIUrl":"10.1016/j.coi.2025.102692","url":null,"abstract":"<div><div>Recent advancements in microbiome research have revealed the restorative capacities of postbiotics, including indole and its derivatives generated via bacterial tryptophan metabolism. Widespread in prokaryotic and eukaryotic communities, indole and its derivatives are uniquely suited to promote host physiology and homeostasis at the host/microbe interface. In addition to suppressing the bacterial pathogenesis, the antioxidant, anti-inflammatory, antidiabetic, antihypertensive, immunomodulatory, and metabolic activities of indole and its derivatives make these postbiotics an attractive therapeutic option. However, their clinical translation is impeded by pharmacokinetic constraints, structural promiscuity, and formulation difficulties. This review examines the current status of indole bioactivities, identifies translational challenges, and suggests the use of artificial intelligence as a method for establishing a comprehensive framework for future translational development.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102692"},"PeriodicalIF":5.8,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508529","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 : 2025-11-10DOI: 10.1016/j.coi.2025.102684
Nicolle Sweeney , Yemil Atisha-Fregoso , Rita Pozovskiy , Lauren Higdon , Mark Anderson , Betty Diamond , William M Ridgway
Autoimmune diseases have, until recently, been treated with relatively broad immunosuppressive regimens. Newer, more focused monoclonal antibody therapies directed to specific targets, for example, anti-TNF or anti-B cell therapies, can produce significant immunosuppression. ‘Remission’ of autoimmune disease that requires ongoing immunosuppression is not an ideal solution. We define a ‘cure’ for autoimmunity as: resolution of disease without ongoing immunosuppressive therapy. Herein, we discuss the possibilities of such a cure, the mechanisms behind such approaches, and obstacles in the setting of representative systemic (systemic lupus erythematosus, or SLE) and organ-specific (type 1 diabetes, T1D) autoimmune diseases. ‘Cure’ of autoimmunity is a remarkably difficult goal and, as illustrated here, will require detailed scientific understanding of each autoimmune disease, even beyond the remarkable advances achieved to date. The basic distinction between autoimmune diseases, in which the target organ is largely destroyed at clinical onset (e.g. T1D), and systemic diseases affecting multiple organs strongly affects how progress can be made towards a cure. In the case of systemic disease, obtaining exact further knowledge of the role of immune cell subsets (e.g. short-lived plasma cells in SLE) is critical. In organ-specific autoimmunity, such as in T1D, improved preclinical detection and characterization of the preclinical immune pathology will be essential.
{"title":"Can we cure autoimmunity?","authors":"Nicolle Sweeney , Yemil Atisha-Fregoso , Rita Pozovskiy , Lauren Higdon , Mark Anderson , Betty Diamond , William M Ridgway","doi":"10.1016/j.coi.2025.102684","DOIUrl":"10.1016/j.coi.2025.102684","url":null,"abstract":"<div><div>Autoimmune diseases have, until recently, been treated with relatively broad immunosuppressive regimens. Newer, more focused monoclonal antibody therapies directed to specific targets, for example, anti-TNF or anti-B cell therapies, can produce significant immunosuppression. ‘Remission’ of autoimmune disease that requires ongoing immunosuppression is not an ideal solution. We define a ‘cure’ for autoimmunity as: <em>resolution of disease without ongoing immunosuppressive therapy</em>. Herein, we discuss the possibilities of such a cure, the mechanisms behind such approaches, and obstacles in the setting of representative systemic (systemic lupus erythematosus, or SLE) and organ-specific (type 1 diabetes, T1D) autoimmune diseases. ‘Cure’ of autoimmunity is a remarkably difficult goal and, as illustrated here, will require detailed scientific understanding of each autoimmune disease, even beyond the remarkable advances achieved to date. The basic distinction between autoimmune diseases, in which the target organ is largely destroyed at clinical onset (e.g. T1D), and systemic diseases affecting multiple organs strongly affects how progress can be made towards a cure. In the case of systemic disease, obtaining exact further knowledge of the role of immune cell subsets (e.g. short-lived plasma cells in SLE) is critical. In organ-specific autoimmunity, such as in T1D, improved preclinical detection and characterization of the preclinical immune pathology will be essential.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102684"},"PeriodicalIF":5.8,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498011","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 : 2025-11-06DOI: 10.1016/j.coi.2025.102689
Jonas Lowack , Alexander PJ Vlaar , Robert B Klanderman , Anna-Linda Peters
Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are leading causes of transfusion-related morbidity and mortality. Despite distinct diagnostic criteria, both syndromes present similarly with respiratory distress and pulmonary edema. In recent research, they increasingly appear to share pathophysiological and immunological features. In this review, we discuss current evidence supporting a spectrum model of pulmonary transfusion reactions, spanning hydrostatic to permeability edema. We highlight key immunological mechanisms in TRALI, including Fc-receptor or complement engagement, and cytokine responses, and explore emerging evidence of immune involvement in TACO. To differentiate, the anti-inflammatory cytokine interleukin (IL)-10 and pro-inflammatory IL-6 emerge as potential biomarkers with diagnostic and therapeutic implications. The underdiagnosis of reverse TRALI and TRALI/TACO overlap further highlights the need for additional mechanistic insight and improved diagnostics. Future work should focus on biomarker-guided phenotyping to improve clinical differentiation and treatment strategies for transfusion-related respiratory complications as a spectrum disorder.
{"title":"Pulmonary transfusion reactions as an immunological spectrum disorder","authors":"Jonas Lowack , Alexander PJ Vlaar , Robert B Klanderman , Anna-Linda Peters","doi":"10.1016/j.coi.2025.102689","DOIUrl":"10.1016/j.coi.2025.102689","url":null,"abstract":"<div><div>Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are leading causes of transfusion-related morbidity and mortality. Despite distinct diagnostic criteria, both syndromes present similarly with respiratory distress and pulmonary edema. In recent research, they increasingly appear to share pathophysiological and immunological features. In this review, we discuss current evidence supporting a spectrum model of pulmonary transfusion reactions, spanning hydrostatic to permeability edema. We highlight key immunological mechanisms in TRALI, including Fc-receptor or complement engagement, and cytokine responses, and explore emerging evidence of immune involvement in TACO. To differentiate, the anti-inflammatory cytokine interleukin (IL)-10 and pro-inflammatory IL-6 emerge as potential biomarkers with diagnostic and therapeutic implications. The underdiagnosis of reverse TRALI and TRALI/TACO overlap further highlights the need for additional mechanistic insight and improved diagnostics. Future work should focus on biomarker-guided phenotyping to improve clinical differentiation and treatment strategies for transfusion-related respiratory complications as a spectrum disorder.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"98 ","pages":"Article 102689"},"PeriodicalIF":5.8,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464760","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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