Pub Date : 2025-10-27DOI: 10.1016/j.coi.2025.102681
Manuel Rojas , Yeny Acosta-Ampudia , Diana M. Monsalve , Carolina Ramı́rez-Santana , Luke S. Heuer , William M. Ridgway , Juan-Manuel Anaya , Zhe-Xiong Lian , M. Eric Gershwin
Infectious agents are potential triggers for autoimmune diseases (ADs) in susceptible individuals, with infection being a key factor in initiating autoimmunity. Epidemiological and experimental evidence suggests molecular mimicry as a plausible mechanism for breaking peripheral tolerance, leading to clinical disease. However, molecular mimicry is not the sole mechanism; other factors, such as deficiencies in central tolerance, bystander activation, epitope spreading, and sustained antigenic stimulation, may also contribute to AD etiology. Advanced methods, including molecular docking simulations, affinity estimation for human leukocyte antigens, and three-dimensional structural analysis of peptides, are increasingly vital for studying molecular mimicry’s role in AD pathogenesis. Further research into peptide conformational analysis is essential for designing effective vaccines and understanding environmental factors in autoimmunity.
{"title":"Autoimmunity, epitope analysis, and molecular mimicry","authors":"Manuel Rojas , Yeny Acosta-Ampudia , Diana M. Monsalve , Carolina Ramı́rez-Santana , Luke S. Heuer , William M. Ridgway , Juan-Manuel Anaya , Zhe-Xiong Lian , M. Eric Gershwin","doi":"10.1016/j.coi.2025.102681","DOIUrl":"10.1016/j.coi.2025.102681","url":null,"abstract":"<div><div>Infectious agents are potential triggers for autoimmune diseases (ADs) in susceptible individuals, with infection being a key factor in initiating autoimmunity. Epidemiological and experimental evidence suggests molecular mimicry as a plausible mechanism for breaking peripheral tolerance, leading to clinical disease. However, molecular mimicry is not the sole mechanism; other factors, such as deficiencies in central tolerance, bystander activation, epitope spreading, and sustained antigenic stimulation, may also contribute to AD etiology. Advanced methods, including molecular docking simulations, affinity estimation for human leukocyte antigens, and three-dimensional structural analysis of peptides, are increasingly vital for studying molecular mimicry’s role in AD pathogenesis. Further research into peptide conformational analysis is essential for designing effective vaccines and understanding environmental factors in autoimmunity.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102681"},"PeriodicalIF":5.8,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396057","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 : 2025-10-23DOI: 10.1016/j.coi.2025.102682
Regina M Antonetti , Manan Shah , Noah S Butler
Malaria is a life-threatening disease affecting more than 200 million people worldwide. CD4 T helper 1 (Th1) and T follicular helper (Tfh) cells are critical for stimulating phagocyte activation and humoral immunity, yet sterilizing, protective immune memory responses rarely develop. Malaria induces unique physiologic changes in the infected host that may give rise to nonconventional Tfh subsets and inefficient memory responses. While our understanding of the differentiation of conventional Tfh cells induced by Plasmodium infection is growing, how and whether malaria-associated environmental cues induce Tfh populations exhibiting mixed phenotype and function are not well defined. Moreover, little is known about the development and function of Tfh memory cells during malaria. In this review, we discuss the phenotype and known functions of Tfh subsets and memory development induced during malaria and highlight key priority knowledge gaps that remain to be addressed.
{"title":"T follicular helper cell development during malaria","authors":"Regina M Antonetti , Manan Shah , Noah S Butler","doi":"10.1016/j.coi.2025.102682","DOIUrl":"10.1016/j.coi.2025.102682","url":null,"abstract":"<div><div>Malaria is a life-threatening disease affecting more than 200 million people worldwide. CD4 T helper 1 (Th1) and T follicular helper (Tfh) cells are critical for stimulating phagocyte activation and humoral immunity, yet sterilizing, protective immune memory responses rarely develop. Malaria induces unique physiologic changes in the infected host that may give rise to nonconventional Tfh subsets and inefficient memory responses. While our understanding of the differentiation of conventional Tfh cells induced by <em>Plasmodium</em> infection is growing, how and whether malaria-associated environmental cues induce Tfh populations exhibiting mixed phenotype and function are not well defined. Moreover, little is known about the development and function of Tfh memory cells during malaria. In this review, we discuss the phenotype and known functions of Tfh subsets and memory development induced during malaria and highlight key priority knowledge gaps that remain to be addressed.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102682"},"PeriodicalIF":5.8,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358343","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 : 2025-10-17DOI: 10.1016/j.coi.2025.102680
Yoshiaki Matsushima , Samuel T Hwang , Scott I Simon
While T cells play a prominent role, polymorphonuclear neutrophils (PMN) are also significant players in the pathogenesis of psoriasis. This review details the mechanobiology of PMN in the amplification of skin inflammation, a process often under-scrutinized compared to T cell pathways. PMN surveillance of skin microcirculation involves selectin-mediated rolling that transitions to stable β2-integrin–mediated arrest. Upon tissue recruitment, PMN trigger the NLRP3 inflammasome and NETosis, releasing neutrophil extracellular traps, proinflammatory cytokines including IL-1β and IL-18, and damage-associated molecular patterns. These mediators promote keratinocyte proliferation and recruit additional waves of PMN that contribute to a positive feedback loop that sustains skin inflammation and hyperproliferation of keratinocytes. Consequently, assays measuring PMN activation provide a sensitive biomarker for the progression of psoriatic disease. Furthermore, therapeutically targeting upstream mechanosignaling pathways presents a novel therapeutic avenue to move beyond conventional strategies that block downstream cytokines critical for immunocompetence.
{"title":"Mechanobiology of neutrophil inflammasome signaling in psoriasis","authors":"Yoshiaki Matsushima , Samuel T Hwang , Scott I Simon","doi":"10.1016/j.coi.2025.102680","DOIUrl":"10.1016/j.coi.2025.102680","url":null,"abstract":"<div><div>While T cells play a prominent role, polymorphonuclear neutrophils (PMN) are also significant players in the pathogenesis of psoriasis. This review details the mechanobiology of PMN in the amplification of skin inflammation, a process often under-scrutinized compared to T cell pathways. PMN surveillance of skin microcirculation involves selectin-mediated rolling that transitions to stable β<sub>2</sub>-integrin–mediated arrest. Upon tissue recruitment, PMN trigger the NLRP3 inflammasome and NETosis, releasing neutrophil extracellular traps, proinflammatory cytokines including IL-1β and IL-18, and damage-associated molecular patterns. These mediators promote keratinocyte proliferation and recruit additional waves of PMN that contribute to a positive feedback loop that sustains skin inflammation and hyperproliferation of keratinocytes. Consequently, assays measuring PMN activation provide a sensitive biomarker for the progression of psoriatic disease. Furthermore, therapeutically targeting upstream mechanosignaling pathways presents a novel therapeutic avenue to move beyond conventional strategies that block downstream cytokines critical for immunocompetence.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102680"},"PeriodicalIF":5.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319080","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 : 2025-10-14DOI: 10.1016/j.coi.2025.102678
Brian Imbiakha , Hana Janova , Michael S Diamond
Neurotropic viruses represent a public health challenge due to their ability to cause severe neurological conditions, including meningitis, encephalitis, and paralysis. Although many studies have investigated the immune responses to viral infections in the brain and other nervous system targets, most have focused on the effects of resident cells, such as microglia and astrocytes, and infiltrating immune cells, including neutrophils, monocytes, and T cells. However, emerging evidence has demonstrated that neurons themselves mount antiviral responses that suppress viral replication directly and enhance the inhibitory functions of adjacent glial and infiltrating immune cells. In this review, we discuss the intrinsic and extrinsic antiviral responses of neurons, highlighting mechanisms by which they detect viruses and initiate inhibitory responses to protect the nervous system from viral invasion and injury.
{"title":"Antiviral responses in peripheral and brain neurons","authors":"Brian Imbiakha , Hana Janova , Michael S Diamond","doi":"10.1016/j.coi.2025.102678","DOIUrl":"10.1016/j.coi.2025.102678","url":null,"abstract":"<div><div>Neurotropic viruses represent a public health challenge due to their ability to cause severe neurological conditions, including meningitis, encephalitis, and paralysis. Although many studies have investigated the immune responses to viral infections in the brain and other nervous system targets, most have focused on the effects of resident cells, such as microglia and astrocytes, and infiltrating immune cells, including neutrophils, monocytes, and T cells. However, emerging evidence has demonstrated that neurons themselves mount antiviral responses that suppress viral replication directly and enhance the inhibitory functions of adjacent glial and infiltrating immune cells. In this review, we discuss the intrinsic and extrinsic antiviral responses of neurons, highlighting mechanisms by which they detect viruses and initiate inhibitory responses to protect the nervous system from viral invasion and injury.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102678"},"PeriodicalIF":5.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305046","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 : 2025-10-13DOI: 10.1016/j.coi.2025.102679
Niamh Logan , Jessica Raja , Elisabetta A Renzoni
Sarcoidosis is a heterogeneous condition, with some presentations associated with spontaneous remission and favourable outcome without treatment. Other presentations, including small fibre neuropathy, arthropathy and sarcoid-associated fatigue, can cause disabling symptoms that may not respond to disease-modifying therapies and must be managed with symptom-based treatments. Sarcoidosis can also present with organ- or life-threatening manifestations, which must be managed with disease-modifying therapies. Glucocorticoids have traditionally been used as first-line therapy, although a recent randomised controlled trial has suggested that methotrexate as sole therapy may be equally effective in pulmonary sarcoidosis, although with delayed efficacy. Growing evidence of glucocorticoid-related toxicities in sarcoid patients is prompting a paradigm shift in treatment towards a ‘less is more’ approach. In this review article, we will outline the current treatment of sarcoidosis with a particular focus on the shift away from the use of prolonged high-dose steroids.
{"title":"Treating sarcoidosis: when less is more","authors":"Niamh Logan , Jessica Raja , Elisabetta A Renzoni","doi":"10.1016/j.coi.2025.102679","DOIUrl":"10.1016/j.coi.2025.102679","url":null,"abstract":"<div><div>Sarcoidosis is a heterogeneous condition, with some presentations associated with spontaneous remission and favourable outcome without treatment. Other presentations, including small fibre neuropathy, arthropathy and sarcoid-associated fatigue, can cause disabling symptoms that may not respond to disease-modifying therapies and must be managed with symptom-based treatments. Sarcoidosis can also present with organ- or life-threatening manifestations, which must be managed with disease-modifying therapies. Glucocorticoids have traditionally been used as first-line therapy, although a recent randomised controlled trial has suggested that methotrexate as sole therapy may be equally effective in pulmonary sarcoidosis, although with delayed efficacy. Growing evidence of glucocorticoid-related toxicities in sarcoid patients is prompting a paradigm shift in treatment towards a ‘less is more’ approach. In this review article, we will outline the current treatment of sarcoidosis with a particular focus on the shift away from the use of prolonged high-dose steroids.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102679"},"PeriodicalIF":5.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294771","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 : 2025-10-10DOI: 10.1016/j.coi.2025.102676
Emmanuelle Godefroy , Frédéric Altare
Allogeneic hematopoietic stem cell transplantation represents a curative treatment of choice for numerous severe hematological malignancies. While donor-derived transplanted T cells can limit disease relapse (GvT/GvL effect), they also induce, in 30–50% of the patients, acute graft-versus-host disease (aGvHD), a severe condition with elevated mortality and comorbidity rates. Gut microbiota composition has been associated with aGvHD outcome. This observation created a substantial research interest, and individual gut microbiota commensals have been acknowledged for their ability to promote immune regulation, both locally and systemically, and thus limit aGvHD-related inflammation. The mechanisms by which commensals support immune homeostasis are being decrypted at a remarkable rate. However, the trillions of micro-organisms comprising the gut microbiome interact, both directly and indirectly, with local immune cells, which is all the more critical in the context of heavy conditioning regimens these patients undergo, themselves damaging mucosal tissues and prompting inflammation. Commensals can help preserve the gut barrier integrity by actively limiting deleterious inflammation processes. Mechanistically deciphering the intricate crosstalk between gut microbes and gut immune cells, both at the species level and globally, represents a colossal challenge, but holds great promise in predicting and harnessing numerous pathological processes, including aGvHD. This review aims to examine the acquired knowledge concerning immunoregulatory responses driven by gut microbiota in the context of aGvHD. Recent preclinical and clinical studies harnessing such pathways proved to be encouraging, while substantial hurdles subsist regarding how to successfully harness this complex host/microbiota interplay to constrain aGvHD.
{"title":"Deciphering and harnessing gut microbiota–associated immune regulation in acute graft-versus-host disease","authors":"Emmanuelle Godefroy , Frédéric Altare","doi":"10.1016/j.coi.2025.102676","DOIUrl":"10.1016/j.coi.2025.102676","url":null,"abstract":"<div><div>Allogeneic hematopoietic stem cell transplantation represents a curative treatment of choice for numerous severe hematological malignancies. While donor-derived transplanted T cells can limit disease relapse (GvT/GvL effect), they also induce, in 30–50% of the patients, acute graft-versus-host disease (aGvHD), a severe condition with elevated mortality and comorbidity rates. Gut microbiota composition has been associated with aGvHD outcome. This observation created a substantial research interest, and individual gut microbiota commensals have been acknowledged for their ability to promote immune regulation, both locally and systemically, and thus limit aGvHD-related inflammation. The mechanisms by which commensals support immune homeostasis are being decrypted at a remarkable rate. However, the trillions of micro-organisms comprising the gut microbiome interact, both directly and indirectly, with local immune cells, which is all the more critical in the context of heavy conditioning regimens these patients undergo, themselves damaging mucosal tissues and prompting inflammation. Commensals can help preserve the gut barrier integrity by actively limiting deleterious inflammation processes. Mechanistically deciphering the intricate crosstalk between gut microbes and gut immune cells, both at the species level and globally, represents a colossal challenge, but holds great promise in predicting and harnessing numerous pathological processes, including aGvHD. This review aims to examine the acquired knowledge concerning immunoregulatory responses driven by gut microbiota in the context of aGvHD. Recent preclinical and clinical studies harnessing such pathways proved to be encouraging, while substantial hurdles subsist regarding how to successfully harness this complex host/microbiota interplay to constrain aGvHD.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102676"},"PeriodicalIF":5.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262435","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 : 2025-10-10DOI: 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}
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