Pub Date : 2025-10-10DOI: 10.1016/j.coi.2025.102675
Simone A Minnie , Melissa M Berrien-Elliott , Melody Smith , Melinda A Biernacki , Marie Bleakley
Allogeneic hematopoietic cell transplantation (HCT) can cure patients with high-risk hematologic malignancies. Donor T and natural killer (NK) cells contribute to graft-versus-leukemia (GVL) effects that provide relapse protection. Post-HCT relapses often represent inadequate GVL, but alloreactive lymphocytes that confer GVL may also cause graft-versus-host-disease (GVHD). Here, we review recent developments to selectively augment GVL while minimizing GVHD. Insights into the unique mechanisms of post-HCT T cell dysfunction highlight interventions to enhance GVL-mediating T cells. Early clinical data suggest that adoptive transfer of engineered donor T cells, expressing either transgenic T cell receptors specific for minor histocompatibility antigens presented exclusively on recipient hematopoietic cells or chimeric antigen receptors binding surface proteins on malignant cells, can mitigate post-HCT relapse. NK cells, key GVL mediators after haploidentical HCT, can be induced into a highly functional memory-like state and administered to HCT recipients to enhance GVL. These innovations promise much-needed improvements in post-HCT outcomes.
{"title":"Optimizing post-transplantation cell therapies to enhance graft-versus-leukemia effects in hematological malignancies","authors":"Simone A Minnie , Melissa M Berrien-Elliott , Melody Smith , Melinda A Biernacki , Marie Bleakley","doi":"10.1016/j.coi.2025.102675","DOIUrl":"10.1016/j.coi.2025.102675","url":null,"abstract":"<div><div>Allogeneic hematopoietic cell transplantation (HCT) can cure patients with high-risk hematologic malignancies. Donor T and natural killer (NK) cells contribute to graft-versus-leukemia (GVL) effects that provide relapse protection. Post-HCT relapses often represent inadequate GVL, but alloreactive lymphocytes that confer GVL may also cause graft-versus-host-disease (GVHD). Here, we review recent developments to selectively augment GVL while minimizing GVHD. Insights into the unique mechanisms of post-HCT T cell dysfunction highlight interventions to enhance GVL-mediating T cells. Early clinical data suggest that adoptive transfer of engineered donor T cells, expressing either transgenic T cell receptors specific for minor histocompatibility antigens presented exclusively on recipient hematopoietic cells or chimeric antigen receptors binding surface proteins on malignant cells, can mitigate post-HCT relapse. NK cells, key GVL mediators after haploidentical HCT, can be induced into a highly functional memory-like state and administered to HCT recipients to enhance GVL. These innovations promise much-needed improvements in post-HCT outcomes.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102675"},"PeriodicalIF":5.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262436","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 : 2025-10-09DOI: 10.1016/j.coi.2025.102674
Yuan Zhou, Xiao-Yong Man
Psoriasis is a chronic immune-mediated skin disease whose inflammation can affect other systems and lead to various comorbidities. As a model inflammatory skin disease, while advances in mechanistic insights and targeted therapies have improved outcomes, unmet clinical needs persist. Modern technologies like single-cell sequencing and spatial transcriptomics reveal that skin immunity operates as a complex network involving neuroregulation, symbiotic microbial immunity, metabolic abnormalities, and reprogramming. These findings underscore the complexity of the local immune microenvironment in the skin and its central role in disease pathogenesis.
In psoriatic inflammation, the epidermal immune microenvironment — driven by keratinocytes, dendritic cells, T cells, and skin microbiota — emerges as a core pathogenic mechanism. Keratinocytes, acting as both inflammatory effectors and disease drivers, interact with immune cells to initiate and amplify responses. Studying this microenvironment offers novel therapeutic targets for psoriasis and related inflammatory skin diseases.
{"title":"The epidermal immune microenvironment plays a central role in the pathogenesis of psoriasis","authors":"Yuan Zhou, Xiao-Yong Man","doi":"10.1016/j.coi.2025.102674","DOIUrl":"10.1016/j.coi.2025.102674","url":null,"abstract":"<div><div>Psoriasis is a chronic immune-mediated skin disease whose inflammation can affect other systems and lead to various comorbidities. As a model inflammatory skin disease, while advances in mechanistic insights and targeted therapies have improved outcomes, unmet clinical needs persist. Modern technologies like single-cell sequencing and spatial transcriptomics reveal that skin immunity operates as a complex network involving neuroregulation, symbiotic microbial immunity, metabolic abnormalities, and reprogramming. These findings underscore the complexity of the local immune microenvironment in the skin and its central role in disease pathogenesis.</div><div>In psoriatic inflammation, the epidermal immune microenvironment — driven by keratinocytes, dendritic cells, T cells, and skin microbiota — emerges as a core pathogenic mechanism. Keratinocytes, acting as both inflammatory effectors and disease drivers, interact with immune cells to initiate and amplify responses. Studying this microenvironment offers novel therapeutic targets for psoriasis and related inflammatory skin diseases.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102674"},"PeriodicalIF":5.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262438","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 : 2025-10-09DOI: 10.1016/j.coi.2025.102677
Ellen F Foxman
A central challenge in defending mucosal barriers is protecting against pathogens while also limiting excessive inflammation. Respiratory viruses are a prime example — respiratory viruses present a threat to their target cells, the epithelial cells that line the airways, but excessive leukocyte recruitment to fight the infection can lead to inflammation and respiratory distress. This review focuses on how epithelial-intrinsic defenses contribute to achieving a balanced antiviral response by adding ‘layers of defense’ that engage in sequence to control infections. Layers include: (1) secreting a defensive extracellular barrier, (2) directly blocking viral replication through cell-intrinsic effector mechanisms, (3) amplifying cell-intrinsic defenses within the epithelium through Type III interferons and other epithelial-specific mechanisms, and (4) coordinating leukocyte recruitment and activation. Recent findings in humans and organoid models support the idea that the ‘layers of defense’ created by epithelial-intrinsic mechanisms frequently and successfully counteract respiratory virus infections and limit their health impact.
{"title":"Layers of defense: protection from respiratory viruses by epithelial-intrinsic immunity","authors":"Ellen F Foxman","doi":"10.1016/j.coi.2025.102677","DOIUrl":"10.1016/j.coi.2025.102677","url":null,"abstract":"<div><div>A central challenge in defending mucosal barriers is protecting against pathogens while also limiting excessive inflammation. Respiratory viruses are a prime example — respiratory viruses present a threat to their target cells, the epithelial cells that line the airways, but excessive leukocyte recruitment to fight the infection can lead to inflammation and respiratory distress. This review focuses on how epithelial-intrinsic defenses contribute to achieving a balanced antiviral response by adding ‘layers of defense’ that engage in sequence to control infections. Layers include: (1) secreting a defensive extracellular barrier, (2) directly blocking viral replication through cell-intrinsic effector mechanisms, (3) amplifying cell-intrinsic defenses within the epithelium through Type III interferons and other epithelial-specific mechanisms, and (4) coordinating leukocyte recruitment and activation. Recent findings in humans and organoid models support the idea that the ‘layers of defense’ created by epithelial-intrinsic mechanisms frequently and successfully counteract respiratory virus infections and limit their health impact.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102677"},"PeriodicalIF":5.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262437","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 : 2025-10-04DOI: 10.1016/j.coi.2025.102673
Mariam Alam , Avrom S. Caplan , Misha Rosenbach
Cutaneous involvement of sarcoidosis can provide important insights into the presence and prognosis of systemic involvement. Recent insights into the underlying pathophysiology of sarcoidosis have allowed for more targeted therapy, including inhibition of the JAK-STAT and mTOR pathways. In this review article, we discuss the epidemiology, clinical presentation, and pathophysiology of cutaneous sarcoidosis and delve into both traditional and evolving treatment strategies, with a focus on the association of therapy with our evolving understanding of sarcoidosis pathophysiology.
{"title":"When granulomatous inflammation becomes visible: insights into cutaneous sarcoidosis","authors":"Mariam Alam , Avrom S. Caplan , Misha Rosenbach","doi":"10.1016/j.coi.2025.102673","DOIUrl":"10.1016/j.coi.2025.102673","url":null,"abstract":"<div><div>Cutaneous involvement of sarcoidosis can provide important insights into the presence and prognosis of systemic involvement. Recent insights into the underlying pathophysiology of sarcoidosis have allowed for more targeted therapy, including inhibition of the JAK-STAT and mTOR pathways. In this review article, we discuss the epidemiology, clinical presentation, and pathophysiology of cutaneous sarcoidosis and delve into both traditional and evolving treatment strategies, with a focus on the association of therapy with our evolving understanding of sarcoidosis pathophysiology.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102673"},"PeriodicalIF":5.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234734","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 : 2025-09-30DOI: 10.1016/j.coi.2025.102661
Anne Godat , Dimitrios Chistoforidis , Thomas Greuter
Inflammatory bowel disease (IBD) represents a chronic inflammation of the gastrointestinal tract that arises from a complex interplay between a dysregulated immune response in genetically predisposed individuals. IBD can further be classified into its two main subtypes, Crohn’s disease and ulcerative colitis. Both subtypes have shown increasing prevalence and incidence rates worldwide, and IBD is now considered a global epidemic. About three million patients are estimated to suffer from this disease, both in the US and Europe, with most of them requiring maintenance treatment including immunosuppressive agents, putting them at risk for opportunistic infections. In 2020, coronavirus disease 2019 (COVID-19) hit the world with a long pandemic period resulting in dramatic numbers of hospitalizations, Intensive care unit (ICU) admissions, and deaths. Patients with chronic illnesses, such as IBD, were rapidly considered to be at an increased risk for both infection and infection-related complications. For IBD and its treatment, however, evidence over the last few years showed no increased risk for SARS-CoV-2 infection or COVID-related complications. In this review, we will discuss the latest insights about COVID-19 in IBD patients with a particular focus on the disease course of COVID-19 and on IBD-related adverse outcomes.
{"title":"COVID-19 and inflammatory bowel disease — what to know","authors":"Anne Godat , Dimitrios Chistoforidis , Thomas Greuter","doi":"10.1016/j.coi.2025.102661","DOIUrl":"10.1016/j.coi.2025.102661","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) represents a chronic inflammation of the gastrointestinal tract that arises from a complex interplay between a dysregulated immune response in genetically predisposed individuals. IBD can further be classified into its two main subtypes, Crohn’s disease and ulcerative colitis. Both subtypes have shown increasing prevalence and incidence rates worldwide, and IBD is now considered a global epidemic. About three million patients are estimated to suffer from this disease, both in the US and Europe, with most of them requiring maintenance treatment including immunosuppressive agents, putting them at risk for opportunistic infections. In 2020, coronavirus disease 2019 (COVID-19) hit the world with a long pandemic period resulting in dramatic numbers of hospitalizations, Intensive care unit (ICU) admissions, and deaths. Patients with chronic illnesses, such as IBD, were rapidly considered to be at an increased risk for both infection and infection-related complications. For IBD and its treatment, however, evidence over the last few years showed no increased risk for SARS-CoV-2 infection or COVID-related complications. In this review, we will discuss the latest insights about COVID-19 in IBD patients with a particular focus on the disease course of COVID-19 and on IBD-related adverse outcomes.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102661"},"PeriodicalIF":5.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208346","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 : 2025-09-22DOI: 10.1016/j.coi.2025.102659
Lucio Verdoni , Angelo Mazza , Laura Martelli , Annalisa Gervasoni , Angela Amoroso , Simona Anna Marcora , Paolo Brambilla , Ezio Bonanomi , Greta Carioli , Lorenzo D’Antiga
Background
During the SARS-CoV-2 pandemic, we described a peak of a Kawasaki-like disease in children, later renamed multisystem inflammatory syndrome in children (MIS-C). We report the long-term outcomes of MIS-C patients who presented to our center.
Methods
We recorded clinical features and outcomes in patients with MIS-C admitted to our institution (February 2020–February 2022), focusing on the long-term outcome of those with a severe course.
Results
A total of 50 MIS-C patients (mean age 8.8 ± 4.3 years, 16 females) were admitted. In univariate analysis, the predictors of high-risk disease were older age; high CRP, neutrophils, ferritin, D-dimer, and transaminases; and low white blood cells, lymphocytes, platelets, albumin, and sodium. In multivariate analysis, a more severe course of the disease was associated with sodium ≤133 or ferritin >684. In two months, the symptoms disappeared. No relapses occurred during four years of surveillance.
Conclusion
The prognosis of MIS-C is favorable, even in severe cases. MIS-C resolves completely as early as eight weeks from onset and is not associated with other events over four years of observation. In our experience, careful and correct stratification in the initial phases has proven essential in setting up the correct treatment, with full recovery in all cases.
{"title":"The outcome of severe MIS-C managed at the Italian epicenter of the SARS-CoV-2 epidemic: a follow-up study of 50 consecutive patients","authors":"Lucio Verdoni , Angelo Mazza , Laura Martelli , Annalisa Gervasoni , Angela Amoroso , Simona Anna Marcora , Paolo Brambilla , Ezio Bonanomi , Greta Carioli , Lorenzo D’Antiga","doi":"10.1016/j.coi.2025.102659","DOIUrl":"10.1016/j.coi.2025.102659","url":null,"abstract":"<div><h3>Background</h3><div>During the SARS-CoV-2 pandemic, we described a peak of a Kawasaki-like disease in children, later renamed multisystem inflammatory syndrome in children (MIS-C). We report the long-term outcomes of MIS-C patients who presented to our center.</div></div><div><h3>Methods</h3><div>We recorded clinical features and outcomes in patients with MIS-C admitted to our institution (February 2020–February 2022), focusing on the long-term outcome of those with a severe course.</div></div><div><h3>Results</h3><div>A total of 50 MIS-C patients (mean age 8.8 ± 4.3 years, 16 females) were admitted. In univariate analysis, the predictors of high-risk disease were older age; high CRP, neutrophils, ferritin, D-dimer, and transaminases; and low white blood cells, lymphocytes, platelets, albumin, and sodium. In multivariate analysis, a more severe course of the disease was associated with sodium ≤133 or ferritin >684. In two months, the symptoms disappeared. No relapses occurred during four years of surveillance.</div></div><div><h3>Conclusion</h3><div>The prognosis of MIS-C is favorable, even in severe cases. MIS-C resolves completely as early as eight weeks from onset and is not associated with other events over four years of observation. In our experience, careful and correct stratification in the initial phases has proven essential in setting up the correct treatment, with full recovery in all cases.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102659"},"PeriodicalIF":5.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118483","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 : 2025-09-19DOI: 10.1016/j.coi.2025.102663
Martin Petrek , Natalia V Rivera
Sarcoidosis is a complex, polygenic, and multifactorial disease characterized by granulomas in affected organs, which are the hallmark of the condition. Genetic susceptibility, environmental influences, and lifestyle factors play key roles in its development. Although the exact molecular mechanisms are not yet fully understood, it is known that the immune system plays a role in mediating the disease. Additionally, sarcoidosis encompasses a group of disease entities (endophenotypes) whose clinical features and progression can be described to help improve understanding of their genetic architecture. In this work, we aim to review recent advances in the genetics and immunopathogenesis of sarcoidosis and explore future directions to improve clinical outcomes and achieve the goals of precision medicine.
{"title":"From genes to granulomas: the genetic blueprint of sarcoidosis","authors":"Martin Petrek , Natalia V Rivera","doi":"10.1016/j.coi.2025.102663","DOIUrl":"10.1016/j.coi.2025.102663","url":null,"abstract":"<div><div>Sarcoidosis is a complex, polygenic, and multifactorial disease characterized by granulomas in affected organs, which are the hallmark of the condition. Genetic susceptibility, environmental influences, and lifestyle factors play key roles in its development. Although the exact molecular mechanisms are not yet fully understood, it is known that the immune system plays a role in mediating the disease. Additionally, sarcoidosis encompasses a group of disease entities (endophenotypes) whose clinical features and progression can be described to help improve understanding of their genetic architecture. In this work, we aim to review recent advances in the genetics and immunopathogenesis of sarcoidosis and explore future directions to improve clinical outcomes and achieve the goals of precision medicine.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102663"},"PeriodicalIF":5.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103212","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 : 2025-09-19DOI: 10.1016/j.coi.2025.102662
Shigeo Fuji , Akihiro Ohmoto
Since its first application in HLA-haploidentical settings, post-transplant cyclophosphamide (PTCy) has become a standard for graft-versus-host disease (GVHD) prophylaxis, with its use expanding to matched and mismatched hematopoietic cell transplantation. Its major clinical advantages include versatility and cost-effectiveness, providing robust GVHD prevention independent of donor type, graft source, or conditioning intensity. The mechanism involves selective depletion of rapidly proliferating alloreactive T-cells, while sparing populations such as regulatory T cells. Current research focuses on optimizing the regimen, including conditioning, timing of calcineurin inhibitor initiation, and PTCy dosage. While the standard dose is 50 mg/kg/day on days +3 and +4, dose reduction is being investigated to mitigate toxicities, such as cardiotoxicity. While data suggest lower doses can hasten engraftment and reduce viral infections without compromising GVHD control, the ultimate impact on the graft-versus-leukemia effect remains to be elucidated.
{"title":"Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis: current status and optimization strategies","authors":"Shigeo Fuji , Akihiro Ohmoto","doi":"10.1016/j.coi.2025.102662","DOIUrl":"10.1016/j.coi.2025.102662","url":null,"abstract":"<div><div>Since its first application in HLA-haploidentical settings, post-transplant cyclophosphamide (PTCy) has become a standard for graft-versus-host disease (GVHD) prophylaxis, with its use expanding to matched and mismatched hematopoietic cell transplantation. Its major clinical advantages include versatility and cost-effectiveness, providing robust GVHD prevention independent of donor type, graft source, or conditioning intensity. The mechanism involves selective depletion of rapidly proliferating alloreactive T-cells, while sparing populations such as regulatory T cells. Current research focuses on optimizing the regimen, including conditioning, timing of calcineurin inhibitor initiation, and PTCy dosage. While the standard dose is 50 mg/kg/day on days +3 and +4, dose reduction is being investigated to mitigate toxicities, such as cardiotoxicity. While data suggest lower doses can hasten engraftment and reduce viral infections without compromising GVHD control, the ultimate impact on the graft-versus-leukemia effect remains to be elucidated.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102662"},"PeriodicalIF":5.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103225","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 : 2025-09-18DOI: 10.1016/j.coi.2025.102660
Lorenzo Del Moro , Enrico Brunetta , M. Eric Gershwin , Carlo Selmi
The dogma of an impenetrable blood–brain barrier (BBB) has given way to the view that resident immune cells within the central nervous system respond to a variety of blood-borne soluble factors, particularly cytokines, and play an important functional role. In particular, microglia cells contribute to the regulation of neuroinflammation, with both protective and pathological roles. Specific microglia activation states variably influence the progression of neuroinflammatory and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Significant evidence indicates that gut microbiota–derived products regulate microglial function across the lifespan and influence the BBB. Myeloperoxidase (MPO) catalyzes the conversion of hydrogen peroxide and chloride ions into hypochlorous acid, a potent oxidant implicated in oxidative tissue damage and modulation of inflammatory signaling. Elevated MPO levels in the central nervous system have been correlated with human disease and the dysregulation of MPO activity in microglia is particularly detrimental, as it amplifies the oxidative stress, disrupts the BBB integrity, and potentiates the neuroinflammatory cascades through the activation of transcription factors like NF-κB. Targeting MPO activity through selective inhibitors or antioxidant strategies may attenuate microglial activation and reduce neuroinflammation, highlighting its potential as a therapeutic target, but the regulatory mechanisms governing MPO expression in microglia and its interplay with other inflammatory mediators remain poorly understood. New research efforts into the relationship between gut microbiota, microglia, MPO, and neuroinflammation are essential to unravel the complexities of neuropathology in a variety of conditions beyond neurodegenerative diseases.
{"title":"Microglia and myeloperoxidase in neuroinflammatory and neurodegenerative diseases","authors":"Lorenzo Del Moro , Enrico Brunetta , M. Eric Gershwin , Carlo Selmi","doi":"10.1016/j.coi.2025.102660","DOIUrl":"10.1016/j.coi.2025.102660","url":null,"abstract":"<div><div>The dogma of an impenetrable blood–brain barrier (BBB) has given way to the view that resident immune cells within the central nervous system respond to a variety of blood-borne soluble factors, particularly cytokines, and play an important functional role. In particular, microglia cells contribute to the regulation of neuroinflammation, with both protective and pathological roles. Specific microglia activation states variably influence the progression of neuroinflammatory and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Significant evidence indicates that gut microbiota–derived products regulate microglial function across the lifespan and influence the BBB. Myeloperoxidase (MPO) catalyzes the conversion of hydrogen peroxide and chloride ions into hypochlorous acid, a potent oxidant implicated in oxidative tissue damage and modulation of inflammatory signaling. Elevated MPO levels in the central nervous system have been correlated with human disease and the dysregulation of MPO activity in microglia is particularly detrimental, as it amplifies the oxidative stress, disrupts the BBB integrity, and potentiates the neuroinflammatory cascades through the activation of transcription factors like NF-κB. Targeting MPO activity through selective inhibitors or antioxidant strategies may attenuate microglial activation and reduce neuroinflammation, highlighting its potential as a therapeutic target, but the regulatory mechanisms governing MPO expression in microglia and its interplay with other inflammatory mediators remain poorly understood. New research efforts into the relationship between <u><u>g</u></u>ut microbiota, microglia, MPO, and neuroinflammation are essential to unravel the complexities of neuropathology in a variety of conditions beyond neurodegenerative diseases.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102660"},"PeriodicalIF":5.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093281","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 : 2025-09-16DOI: 10.1016/j.coi.2025.102658
Ashley M Feldkamp , Siba P Raychaudhuri
Psoriatic arthritis (PsA) is a multifaceted autoimmune condition that affects the peripheral and axial joints, entheses, skin, and nails. The management of PsA relies on prompt diagnosis and early initiation of effective treatment to minimize joint destruction. Treatment options for PsA are rapidly evolving and emerging. This review will discuss screening tools, early diagnosis/outcome measures, and treatment guidelines for PsA, including the most recent EULAR/GRAPPA/ACR recommendations. Advances in science and technology are also rapidly changing the landscape of medicine, and we have discussed how targeted therapies, smartphone monitoring, and artificial intelligence could benefit PsA monitoring and treatment. Finally, we discussed the concept of treating PsA as a multisystem disorder with a multidisciplinary team of specialists and implementation of a ‘Total Care’ program. Overall, this review highlights the evolving treatment frameworks in PsA, advocating for early detection, comprehensive assessment, and targeted therapy that can improve patient outcomes and quality of life.
{"title":"Advances in treatment of psoriatic arthritis: current guidelines and emerging therapies","authors":"Ashley M Feldkamp , Siba P Raychaudhuri","doi":"10.1016/j.coi.2025.102658","DOIUrl":"10.1016/j.coi.2025.102658","url":null,"abstract":"<div><div>Psoriatic arthritis (PsA) is a multifaceted autoimmune condition that affects the peripheral and axial joints, entheses, skin, and nails. The management of PsA relies on prompt diagnosis and early initiation of effective treatment to minimize joint destruction. Treatment options for PsA are rapidly evolving and emerging. This review will discuss screening tools, early diagnosis/outcome measures, and treatment guidelines for PsA, including the most recent EULAR/GRAPPA/ACR recommendations. Advances in science and technology are also rapidly changing the landscape of medicine, and we have discussed how targeted therapies, smartphone monitoring, and artificial intelligence could benefit PsA monitoring and treatment. Finally, we discussed the concept of treating PsA as a multisystem disorder with a multidisciplinary team of specialists and implementation of a ‘Total Care’ program. Overall, this review highlights the evolving treatment frameworks in PsA, advocating for early detection, comprehensive assessment, and targeted therapy that can improve patient outcomes and quality of life.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102658"},"PeriodicalIF":5.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082926","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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