Fanny Saidoune, Ahmad Yatim, Jeremy Di Domizio, Michel Gilliet
{"title":"Skin manifestations of SARS-CoV-2 infection and its vaccination","authors":"Fanny Saidoune, Ahmad Yatim, Jeremy Di Domizio, Michel Gilliet","doi":"10.1016/j.coi.2025.102656","DOIUrl":"10.1016/j.coi.2025.102656","url":null,"abstract":"<div><div>SARS-CoV-2 infection and vaccination are associated with a broad range of skin manifestations, including chilblains, urticaria, morbilliform and papulovesicular rashes, purpuric-necrotic lesions, and autoimmune flares. These patterns reflect differences in the timing and nature of type I interferon (IFN-I) responses. Rapid TLR7-mediated IFN-I production by plasmacytoid dendritic cells (pDCs) in the upper airways restricts viral replication; hyperresponsive pDCs protect from severe infection but may cause chilblain-like lesions through exaggerated local inflammation. When early IFN-I responses are weak, viral spread to the lungs triggers endothelial cell death, mitochondrial DNA release, and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation, producing a late IFN-I surge that amplifies inflammation, mirrored by morbilliform, vesicular, or necrotic skin lesions. mRNA and viral vector vaccines can similarly activate nucleic acid sensors, inducing IFN-I–driven rashes, and promote spike-specific T cells that cross-react with skin antigens. Recognizing these cutaneous signs offers insight into the balance between protective and pathogenic immunity in COVID-19.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102656"},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045726","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}
Yoshiaki Matsushima , Samuel T Hwang , Scott I Simon
{"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":"2025-12-01","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}
{"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":"2025-12-01","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}
Zihan Ma , Richard W Pierce , Carrie L Lucas , Clara Abraham , Carlos Fernandez-Hernando , Dan Jane-wit
{"title":"Roles of endothelial cells during infection","authors":"Zihan Ma , Richard W Pierce , Carrie L Lucas , Clara Abraham , Carlos Fernandez-Hernando , Dan Jane-wit","doi":"10.1016/j.coi.2025.102648","DOIUrl":"10.1016/j.coi.2025.102648","url":null,"abstract":"<div><div>Endothelial cells (ECs) integrate immune and vascular functions to promote host defense against pathogens. While previously studied as forming passive flow conduits, ECs are now recognized as active contributors to maladaptive inflammation. During acute infection, ECs may promote tissue pathologies, including hypoxia, acidosis, electrolyte disturbances, and capillary barrier breakdown. These pathologies significantly contribute to organ dysfunction and septic shock. In chronic vascular infection, ECs may promote loss of vascular quiescence, contributing to vascular malformations and vaso-occlusive lesions. In this review, we discuss the interplay between the immune and vascular roles of blood ECs, an emerging area of interest with therapeutic implications. While previously overlooked, therapies targeting dysregulation of EC function(s) may show clinical benefit towards improving outcomes related to both acute and chronic forms of infection.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102648"},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"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":"2025-12-01","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}
{"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":"2025-12-01","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}
{"title":"Complement in systemic lupus erythematosus across time and space: from tolerance to tissue injury and from extracellular to intracellular functions","authors":"Giovanna Clavarino , Jeanne Vigne , Marie-Sophie Meuleman , Axelle Amen , Véronique Rossi , Chantal Dumestre-Pérard","doi":"10.1016/j.coi.2025.102655","DOIUrl":"10.1016/j.coi.2025.102655","url":null,"abstract":"<div><div>The complement system plays a paradoxical role in systemic lupus erythematosus physiopathology, acting both as a protective mechanism and as a driver of tissue injury, depending on disease stage. Neutrophil extracellular traps (NETs) further exacerbate disease activity by promoting complement activation and autoantigen exposure, forming an amplifying inflammatory loop. Lupus nephritis remains challenging to monitor using conventional complement biomarkers such as CH50, C3, and C4; the utility of anti-C1q, anti-ficolin, and anti-C1s antibodies, along with tissue-based markers such as renal C4d and C5b-9 deposits, as markers of disease activity and prognosis, is discussed. Interestingly, noncanonical functions of complement, including intracellular roles in immune cell metabolism regulation, have been recently described. Understanding the crosstalk between complement, NETs, and immune metabolism may provide new targets for therapeutic intervention.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"97 ","pages":"Article 102655"},"PeriodicalIF":5.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"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":"2025-12-01","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}
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
{"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":"2025-12-01","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}
{"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":"2025-12-01","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}