{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:35:15Z","timestamp":1791848115530,"version":"4.3.4"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Multisystem Inflammatory Syndrome in Children (MIS-C) is a serious condition emerging during the COVID-19 pandemic, strongly associated with prior SARS-CoV-2 infection. Characterized by systemic inflammation affecting multiple organs, MIS-C presents a complex clinical picture including fever, gastrointestinal distress, cardiac dysfunction, and neurological manifestations. Although its exact pathogenesis remains incompletely understood, immune dysregulation is recognized as a central mechanism. This review examines current understanding of MIS-C pathogenesis, focusing on immune dysfunction and viral triggers, particularly SARS-CoV-2. We analyze both innate and adaptive immune responses, cytokine storm dynamics, molecular mimicry, and virus-induced inflammatory cascades. Additionally, we discuss potential immunomodulatory therapeutic strategies and identify future research directions to improve MIS-C management and treatment outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1624963","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:35:08Z","timestamp":1764138908000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["MIS-C pathogenesis: immune dysregulation &amp; viral triggers"],"prefix":"10.3389","volume":"16","author":[{"given":"Tiantian","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyuan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junye","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-021-00963-4","article-title":"Clinical characteristics of paediatric hyperinflammatory syndrome in the era of corona virus disease 2019 (COVID-19)","volume":"36","author":"Basu","year":"2021","journal-title":"Indian J Clin Biochem"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s13312-020-1997-1","article-title":"Hyperinflammatory syndrome in children associated with COVID-19: need for awareness","volume":"57","author":"Bhat","year":"2020","journal-title":"Indian Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5711","DOI":"10.3390\/ijms24065711","article-title":"Immunology of multisystem inflammatory syndrome after COVID-19 in children: A review of the current evidence","volume":"24","author":"Filippatos","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.747190","article-title":"The spectrum of manifestations of severe acute respiratory syndrome-coronavirus 2 (SARS-coV2) infection in children: what we can learn from multisystem inflammatory syndrome in children (MIS-C)","volume":"8","author":"Panaro","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)31103-x","article-title":"An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study","volume":"395","author":"Verdoni","year":"2020","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021680","article-title":"Multisystem inflammatory syndrome in U.S. Children and adolescents","volume":"383","author":"Feldstein","year":"2020","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.10369","article-title":"Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-coV-2","volume":"324","author":"Whittaker","year":"2020","journal-title":"Jama"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.888897","article-title":"Dysregulated interferon response and immune hyperactivation in severe COVID-19: targeting STATs as a novel therapeutic strategy","volume":"13","author":"Eskandarian Boroujeni","year":"2022","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/tropej\/fmac068","article-title":"Clinico-laboratory profile, intensive care needs and short-term outcome of multisystem inflammatory syndrome in children (MIS-C): experience during first and second waves from north India","volume":"68","author":"Angurana","year":"2022","journal-title":"J Trop Pediatr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.cell.2020.09.034","article-title":"Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C)","volume":"183","author":"Gruber","year":"2020","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.pedneo.2023.05.002","article-title":"Pathophysiological and clinical point of view on Kawasaki disease and MIS-C","volume":"64","author":"Va\u0148kov\u00e1","year":"2023","journal-title":"Pediatr Neonatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00709-9","article-title":"Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison","volume":"17","author":"Sharma","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/aco.0000000000001024","article-title":"The multisystem inflammatory syndrome in children and its association to SARS-CoV-2","volume":"34","author":"Piekarski","year":"2021","journal-title":"Curr Opin Anaesthesiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(20)30651-4","article-title":"COVID-19 and multisystem inflammatory syndrome in children and adolescents","volume":"20","author":"Jiang","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-021-03993-5","article-title":"Multisystem inflammatory syndrome in children related to COVID-19: a systematic review","volume":"180","author":"Hoste","year":"2021","journal-title":"Eur J Pediatr"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1002\/art.42062","article-title":"American college of rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-coV-2 and hyperinflammation in pediatric COVID-19: version 3","volume":"74","author":"Henderson","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s11882-022-01031-4","article-title":"Multisystem inflammatory syndrome in children (MIS-C)","volume":"22","author":"Patel","year":"2022","journal-title":"Curr Allergy Asthma Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2021.05.076","article-title":"Multisystem inflammatory syndrome in children with COVID-19","volume":"49","author":"Gottlieb","year":"2021","journal-title":"Am J Emerg Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"980","DOI":"10.3390\/children10060980","article-title":"Multi-inflammatory syndrome in children (MIS-C) in 2023: is it time to forget about it","volume":"10","author":"La Torre","year":"2023","journal-title":"Children (Basel)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1054-6","article-title":"Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection","volume":"26","author":"Carter","year":"2020","journal-title":"Nat Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.jaci.2022.09.006","article-title":"Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort","volume":"150","author":"Rey-Jurado","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"6632","DOI":"10.3390\/jcm13226632","article-title":"Multisystem inflammatory syndrome of adults (MIS-A) as delayed severe presentation of SARS-coV-2 infection: A description of two cases","volume":"13","author":"Raffeiner","year":"2024","journal-title":"J Clin Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1068301","article-title":"Case Report: A case of multisystem inflammatory syndrome in an 11-year-old female after COVID-19 inactivated vaccine","volume":"11","author":"Saeed","year":"2023","journal-title":"Front Pediatr"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.3390\/children9081238","article-title":"Adrenal crisis mimicking COVID-19 encephalopathy in a teenager with craniopharyngioma","volume":"9","author":"Chien","year":"2022","journal-title":"Children (Basel)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2020.117283","article-title":"Neurological presentations of COVID-19: Findings from the Spanish Society of Neurology neuroCOVID-19 registry","volume":"423","author":"Garc\u00eda-Azor\u00edn","year":"2021","journal-title":"J Neurol Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4103\/jfmpc.jfmpc_941_21","article-title":"Identification of hematological and inflammatory parameters associated with disease severity in hospitalized patients of COVID-19","volume":"11","author":"Sana","year":"2022","journal-title":"J Family Med Prim Care"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1177\/03000605211059939","article-title":"Coagulation profile and correlation between D-dimer, inflammatory markers, and COVID-19 severity in an Indonesian national referral hospital","volume":"49","author":"Sukrisman","year":"2021","journal-title":"J Int Med Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26951","article-title":"The inflammatory markers of multisystem inflammatory syndrome in children (MIS-C) and adolescents associated with COVID-19: A meta-analysis","volume":"93","author":"Zhao","year":"2021","journal-title":"J Med Virol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.29271\/jcpsp.2024.06.727","article-title":"Multisystem inflammatory syndrome in neonates associated with COVID-19 in neonatal ICU of a tertiary care hospital","volume":"34","author":"Shabbir","year":"2024","journal-title":"J Coll Physicians Surg Pak"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1097\/inf.0000000000003449","article-title":"Distinguishing multisystem inflammatory syndrome in children from COVID-19, kawasaki disease and toxic shock syndrome","volume":"41","author":"Godfred-Cato","year":"2022","journal-title":"Pediatr Infect Dis J"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e2116420","DOI":"10.1001\/jamanetworkopen.2021.16420","article-title":"Incidence of multisystem inflammatory syndrome in children among US persons infected with SARS-coV-2","volume":"4","author":"Payne","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B32","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s10020-022-00583-5","article-title":"Host genetic susceptibility underlying SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Brazilian Children","volume":"28","author":"Santos-Rebou\u00e7as","year":"2022","journal-title":"Mol Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jpeds.2020.08.003","article-title":"Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2: A systematic review","volume":"226","author":"Abrams","year":"2020","journal-title":"J Pediatr"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2022.0089","article-title":"Quantitative antibody levels against SARS-coV-2 spike protein in COVID-19 and multisystem inflammatory syndrome in children","volume":"35","author":"Avcu","year":"2022","journal-title":"Viral Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"8269","DOI":"10.3390\/ijerph18168269","article-title":"A systematic review of characteristics associated with COVID-19 in children with typical presentation and with multisystem inflammatory syndrome","volume":"18","author":"Kornitzer","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B36","doi-asserted-by":"publisher","first-page":"13382","DOI":"10.3390\/ijerph192013382","article-title":"Comparison of long-term complications of COVID-19 illness among a diverse sample of children by MIS-C status","volume":"19","author":"Messiah","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B37","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJMoa2102605","article-title":"Multisystem inflammatory syndrome in children - initial therapy and outcomes","volume":"385","author":"Son","year":"2021","journal-title":"N Engl J Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.reumae.2024.01.005","article-title":"Comparison of plasma inflammatory biomarkers between MIS-C and potentially serious infections in pediatric patients","volume":"20","author":"Visa-Re\u00f1\u00e9","year":"2024","journal-title":"Reumatol Clin (Engl Ed)"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1515\/dx-2024-0013","article-title":"Diagnostic value of D-dimer in differentiating multisystem inflammatory syndrome in Children (MIS-C) from Kawasaki disease: systematic literature review and meta-analysis","volume":"11","author":"Lippi","year":"2024","journal-title":"Diagnosis (Berl)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1177\/02683555241261321","article-title":"Elevation of cardiac enzymes and B-type natriuretic peptides following venous recanalization and stenting in chronic venous obstruction","volume":"39","author":"Yan","year":"2024","journal-title":"Phlebology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"113","DOI":"10.4103\/jrms.JRMS_1195_20","article-title":"Myocardial damage in multisystem inflammatory syndrome associated with COVID-19 in children and adolescents","volume":"26","author":"Vukomanovic","year":"2021","journal-title":"J Res Med Sci"},{"key":"B42","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jaut.2017.03.009","article-title":"Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases","volume":"83","author":"Chen","year":"2017","journal-title":"J Autoimmun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01027","article-title":"T cell metabolism: A new perspective on th17\/treg cell imbalance in systemic lupus erythematosus","volume":"11","author":"Shan","year":"2020","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08697-6","article-title":"TGF\u03b2 links EBV to multisystem inflammatory syndrome in children","volume":"640","author":"Goetzke","year":"2025","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010722117","article-title":"Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation","volume":"117","author":"Cheng","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/jci151520","article-title":"The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children","volume":"131","author":"Porritt","year":"2021","journal-title":"J Clin Invest"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07722-4","article-title":"Molecular mimicry in multisystem inflammatory syndrome in children","volume":"632","author":"Bodansky","year":"2024","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.05.014","article-title":"Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease","volume":"1843","author":"Turner","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737772","article-title":"Historical insights into cytokines","author":"Dinarello","year":"2007","journal-title":"Eur J Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"9365","DOI":"10.3390\/ijms26199365","article-title":"Special issue: autoimmune diseases: A swing dance of immune cells","volume":"26","author":"Dzhambazov","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nm939","article-title":"TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases","volume":"9","author":"Feldmann","year":"2003","journal-title":"Nat Med"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)31472-1","article-title":"Pathogenetic insights from the treatment of rheumatoid arthritis","volume":"389","author":"McInnes","year":"2017","journal-title":"Lancet"},{"key":"B53","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13036-025-00534-8","article-title":"Targeting rheumatoid arthritis: a molecular perspective on biologic therapies and clinical progress","volume":"19","author":"Jain","year":"2025","journal-title":"J Biol Eng"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/art.43376","article-title":"Cytokine pathways driving diverse tissue pathologies in rheumatoid arthritis","author":"Najm","year":"2025","journal-title":"Arthritis Rheumatol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s13075-025-03659-9","article-title":"Treg cells mitigate inflammatory responses and symptoms via \u03b22-AR\/\u03b2-Arr2\/ERK signaling in an experimental rheumatoid arthritis","volume":"27","author":"Liu","year":"2025","journal-title":"Arthritis Res Ther"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2023.134217","article-title":"The pathogenesis and regulatory role of HIF-1 in rheumatoid arthritis","volume":"48","author":"Li","year":"2023","journal-title":"Cent Eur J Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.joca.2017.10.013","article-title":"Hierarchical, imbalanced pro-inflammatory cytokine networks govern the pathogenesis of chronic arthropathies","volume":"26","author":"Livshits","year":"2018","journal-title":"Osteoarthritis Cartilage"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13043","article-title":"Autoimmunity in motion: Mechanisms of immune regulation and destruction revealed by in vivo imaging","volume":"306","author":"Jacobelli","year":"2022","journal-title":"Immunol Rev"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8816041","article-title":"Th17 cells in inflammatory bowel disease: cytokines, plasticity, and therapies","volume":"2021","author":"Zhao","year":"2021","journal-title":"J Immunol Res"},{"key":"B60","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s00011-025-02084-7","article-title":"Interleukin 15 and autoimmune disorders: pathophysiology, therapeutic potential, and clinical implications","volume":"74","author":"Darouni","year":"2025","journal-title":"Inflammation Res"},{"key":"B61","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41392-024-01952-8","article-title":"Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders","volume":"9","author":"Song","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-025-01514-5","article-title":"Inhibition of LARP4-mediated quiescence exit of naive CD4(+) T cells ameliorates autoimmune and allergic diseases","author":"Zhou","year":"2025","journal-title":"Nat BioMed Eng"},{"key":"B63","doi-asserted-by":"publisher","first-page":"4025","DOI":"10.1016\/j.cell.2025.06.004","article-title":"Proximity between LAG-3 and the T cell receptor guides suppression of T cell activation and autoimmunity","volume":"188","author":"Du","year":"2025","journal-title":"Cell"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf064","article-title":"B and T cell tolerance and autoimmunity in autoantibody transgenic mice","volume":"14","author":"Yan","year":"2002","journal-title":"Int Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545810","article-title":"Chronic bacterial infection activates autoreactive B cells and induces isotype switching and autoantigen-driven mutations","volume":"46","author":"Jung","year":"2016","journal-title":"Eur J Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1136\/postgradmedj-2011-130364","article-title":"A B cell explanation for autoimmune disease: the forbidden clone returns","volume":"88","author":"McQueen","year":"2012","journal-title":"Postgrad Med J"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08049-w","article-title":"Neuropeptide signalling orchestrates T cell differentiation","volume":"635","author":"Hou","year":"2024","journal-title":"Nature"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e0143715","DOI":"10.1371\/journal.pone.0143715","article-title":"The role of regulatory CD4 T cells in maintaining tolerance in a mouse model of autoimmune hepatitis","volume":"10","author":"An Haack","year":"2015","journal-title":"PloS One"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.05.010","article-title":"Regulatory T cells and inflammatory mediators in autoimmune disease","volume":"142","author":"Gouirand","year":"2022","journal-title":"J Invest Dermatol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114624","article-title":"Exploiting regulatory T cells (Tregs): Cutting-edge therapy for autoimmune diseases","volume":"155","author":"Hassan","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2025.06.007","article-title":"Breaking tolerance: an update of Treg dysfunction in autoimmunity","volume":"46","author":"Cheru","year":"2025","journal-title":"Trends Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-025-00125-0","article-title":"PMEPA1-mediated treg cell impairment promotes endometrial stromal invasion via excessive PI3K\/AKT signaling in endometriosis","volume":"45","author":"Peng","year":"2025","journal-title":"Curr Med Sci"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2021.04.021","article-title":"Mechanistic understanding of innate and adaptive immune responses in SARS-CoV-2 infection","volume":"135","author":"Balkhi","year":"2021","journal-title":"Mol Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01104-y","article-title":"SARS-CoV-2 and innate immunity: the good, the bad, and the \u201cgoldilocks","volume":"21","author":"Sievers","year":"2024","journal-title":"Cell Mol Immunol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1159326","article-title":"Innate and adaptive immunity to SARS-CoV-2 and predisposing factors","volume":"14","author":"Shen","year":"2023","journal-title":"Front Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.07.005","article-title":"Lessons for COVID-19 immunity from other coronavirus infections","volume":"53","author":"Sariol","year":"2020","journal-title":"Immunity"},{"key":"B77","doi-asserted-by":"publisher","first-page":"e107826","DOI":"10.15252\/embj.2021107826","article-title":"SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation","volume":"40","author":"Thorne","year":"2021","journal-title":"EMBO J"},{"key":"B78","doi-asserted-by":"publisher","first-page":"3810","DOI":"10.1038\/s41467-020-17665-9","article-title":"Activation and evasion of type I interferon responses by SARS-CoV-2","volume":"11","author":"Lei","year":"2020","journal-title":"Nat Commun"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced host response to SARS-coV-2 drives development of COVID-19","volume":"181","author":"Blanco-Melo","year":"2020","journal-title":"Cell"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc8511","article-title":"Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications","volume":"369","author":"Mathew","year":"2020","journal-title":"Science"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-023-1044-4","article-title":"Cytokine storm and translating IL-6 biology into effective treatments for COVID-19","volume":"17","author":"Li","year":"2023","journal-title":"Front Med"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-02051-0","article-title":"T cell immune evasion by SARS-CoV-2 JN.1 escapees targeting two cytotoxic T cell epitope hotspots","volume":"26","author":"Tian","year":"2025","journal-title":"Nat Immunol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"e04690","DOI":"10.1002\/advs.202504690","article-title":"Engineered dual-function antibody-like proteins to combat SARS-coV-2-induced immune dysregulation and inflammation","volume":"12","author":"Wang","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B84","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.clinph.2022.10.017","article-title":"Co-ultramicronized palmitoylethanolamide\/luteolin normalizes GABA-ergic activity and cortical plasticity in long COVID-19 syndrome","volume":"145","author":"Versace","year":"2023","journal-title":"Clin Neurophysiol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3906\/sag-2005-287","article-title":"COVID-19: pathogenesis, genetic polymorphism, clinical features and laboratory findings","volume":"50","author":"\u00d6zt\u00fcrk","year":"2020","journal-title":"Turk J Med Sci"},{"key":"B86","doi-asserted-by":"publisher","first-page":"e29012","DOI":"10.1002\/jmv.29012","article-title":"Epidemic history and evolution of an emerging threat of international concern, the severe acute respiratory syndrome coronavirus 2","volume":"95","author":"Giovanetti","year":"2023","journal-title":"J Med Virol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)31094-1","article-title":"Hyperinflammatory shock in children during COVID-19 pandemic","volume":"395","author":"Riphagen","year":"2020","journal-title":"Lancet"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021756","article-title":"Multisystem inflammatory syndrome in children in new york state","volume":"383","author":"Dufort","year":"2020","journal-title":"N Engl J Med"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinsp.2025.100648","article-title":"Clinical characteristics, SARS-CoV-2 variants, and outcomes of adults hospitalized due to COVID-19 in Latin American countries","volume":"80","author":"L\u00f3pez-Mac\u00edas","year":"2025","journal-title":"Clinics (Sao Paulo)"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellin.2022.100029","article-title":"Emerging SARS-CoV-2 variants: Why, how, and what\u2019s next","volume":"1","author":"Chen","year":"2022","journal-title":"Cell Insight"},{"key":"B91","doi-asserted-by":"publisher","first-page":"e29165","DOI":"10.1097\/md.0000000000029165","article-title":"Omicron SARS-CoV-2 variant of concern: A review on its transmissibility, immune evasion, reinfection, and severity","volume":"101","author":"Mohsin","year":"2022","journal-title":"Med (Baltimore)"},{"key":"B92","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1186\/s12879-023-08328-3","article-title":"Role of previous infection with SARS-CoV-2 in protecting against omicron reinfections and severe complications of COVID-19 compared to pre-omicron variants: a systematic review","volume":"23","author":"Arabi","year":"2023","journal-title":"BMC Infect Dis"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.cell.2020.08.012","article-title":"Deep mutational scanning of SARS-coV-2 receptor binding domain reveals constraints on folding and ACE2 binding","volume":"182","author":"Starr","year":"2020","journal-title":"Cell"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69091","article-title":"N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2","volume":"10","author":"Tian","year":"2021","journal-title":"Elife"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf3698","article-title":"Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection","volume":"5","author":"Reynolds","year":"2020","journal-title":"Sci Immunol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1016\/j.cell.2021.02.010","article-title":"Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection","volume":"184","author":"Anderson","year":"2021","journal-title":"Cell"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7050e1","article-title":"SARS-coV-2 B.1.1.529 (Omicron) variant - United States, december 1-8, 2021","volume":"70","year":"2021","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.790273","article-title":"Mechanisms of immune dysregulation in COVID-19 are different from SARS and MERS: A perspective in context of kawasaki disease and MIS-C","volume":"10","author":"Dhaliwal","year":"2022","journal-title":"Front Pediatr"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1111\/cea.14425","article-title":"Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection","volume":"54","author":"Tian","year":"2024","journal-title":"Clin Exp Allergy"},{"key":"B100","doi-asserted-by":"publisher","first-page":"e80964","DOI":"10.7759\/cureus.80964","article-title":"Human metapneumovirus: emergence, impact, and public health significance","volume":"17","author":"Mistry","year":"2025","journal-title":"Cureus"},{"key":"B101","doi-asserted-by":"publisher","first-page":"990","DOI":"10.3390\/v13060990","article-title":"High frequency of viral co-detections in acute bronchiolitis","volume":"13","author":"Petat","year":"2021","journal-title":"Viruses"},{"key":"B102","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41584-025-01244-7","article-title":"A role for TGF\u03b2 and EBV in MIS-C pathogenesis","volume":"21","author":"Papatriantafyllou","year":"2025","journal-title":"Nat Rev Rheumatol"},{"key":"B103","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1016\/j.jaci.2024.11.029","article-title":"Features of hyperinflammation link the biology of Epstein-Barr virus infection and cytokine storm syndromes","volume":"155","author":"Liu","year":"2025","journal-title":"J Allergy Clin Immunol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.55730\/1300-0144.5905","article-title":"A new scoring in differential diagnosis: multisystem inflammatory syndrome or adenovirus infection","volume":"54","author":"Gen\u00e7eli","year":"2024","journal-title":"Turk J Med Sci"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.2091","article-title":"Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19","volume":"325","author":"Feldstein","year":"2021","journal-title":"Jama"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.654587","article-title":"Plasmacytoid dendritic cells depletion and elevation of IFN-\u03b3 Dependent chemokines CXCL9 and CXCL10 in children with multisystem inflammatory syndrome","volume":"12","author":"Caldarale","year":"2021","journal-title":"Front Immunol"},{"key":"B107","doi-asserted-by":"publisher","first-page":"e0266336","DOI":"10.1371\/journal.pone.0266336","article-title":"Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study","volume":"17","author":"Biesbroek","year":"2022","journal-title":"PloS One"},{"key":"B108","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1001\/jamapediatrics.2024.5466","article-title":"Six-month outcomes in the long-term outcomes after the multisystem inflammatory syndrome in children study","volume":"179","author":"Truong","year":"2025","journal-title":"JAMA Pediatr"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1093\/lifemedi\/lnae034","article-title":"The complex landscape of immune dysregulation in multisystem inflammatory syndrome in children with COVID-19","volume":"3","author":"Guo","year":"2024","journal-title":"Life Med"},{"key":"B110","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3390\/children7070069","article-title":"Multi-system inflammatory syndrome in children (MIS-C) following SARS-coV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management","volume":"7","author":"Nakra","year":"2020","journal-title":"Children (Basel)"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11478","article-title":"Treatment of multisystem inflammatory syndrome in children: understanding differences in results of comparative effectiveness studies","volume":"4","author":"Melgar","year":"2022","journal-title":"ACR Open Rheumatol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-024-05586-4","article-title":"Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study","volume":"183","author":"Schwartz","year":"2024","journal-title":"Eur J Pediatr"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2024.126499","article-title":"Multisystem inflammatory syndrome in children (MIS-C) cases by vaccination status in California","volume":"43","author":"Le Marchand","year":"2025","journal-title":"Vaccine"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/s2352-4642(23)00078-0","article-title":"Safety and effectiveness of vaccines against COVID-19 in children aged 5\u201311 years: a systematic review and meta-analysis","volume":"7","author":"Piechotta","year":"2023","journal-title":"Lancet Child Adolesc Health"},{"key":"B115","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1007\/s00431-025-06253-y","article-title":"Two-year follow-up on multisystem inflammatory syndrome in children (MIS-c): findings from a tertiary paediatric hospital in Latvia","volume":"184","author":"Roge-Gurecka","year":"2025","journal-title":"Eur J Pediatr"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1624963\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:35:08Z","timestamp":1764138908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1624963\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":115,"alternative-id":["10.3389\/fimmu.2025.1624963"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1624963","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]},"article-number":"1624963"}}