{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:09:00Z","timestamp":1790392140297,"version":"4.1.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Glycosylation is a post-translational modification that plays a crucial role in immune system activity. Phosphomannomutase 2-Congenital Disorder of Glycosylation (PMM2-CDG) is a rare genetic disease affecting glycosylation with a multi-systemic impact. PMM2-CDG patients commonly show immune disfunction and elevated pro-inflammatory cytokine levels that may link to other symptoms. However, the underlying immune mechanisms remain unclear. Given Tumour Necrosis Factor (TNF)\u2019s key role in inflammation, this study proposes that defective glycosylation of its receptors disrupts intracellular signalling, leading to changes in the immune response of PMM2-CDG patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To address this, we applied an integrative approach, combining transcriptomics, glycomics, and immune-related assays to investigate the impact of TNF-a stimulation via TNF receptor 1 (TNFR1) in a cohort of PMM2-CDG patients\u2019 skin fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results reveal a multifaceted disruption of TNF-a signalling in PMM2-CDG fibroblasts. We observed structural abnormalities in TNFR1, including altered receptor shedding. PMM2-CDG cells also showed an altered N-glycosylation profile, affecting particularly, high mannose N-glycans. At transcriptional level, PMM2-CDG cells, especially those bearing the R141H heterozygous variant, exhibited a distinct gene expression profile, after stimulation, characterized by dysregulation of immune and signalling pathways. Functionally, these molecular alterations translated into a diminished secretion of key inflammation and infection mediators, such as interleukin-6 (IL-6) and C-C Motif chemokine ligand 5 (CCL5) upon TNF-a stimulation. Similarly, essential signalling kinases including extracellular-signal-regulated kinase (ERK) 1\/2, p38 and c-Jun N- terminal kinase (JNK) 2 showed reduced expression in PMM2-CDG cells, and their expression did not alter following TNF-a stimulation, unlike control cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conslusion<\/jats:title>\n                    <jats:p>Our findings point to TNFR1 signalling dysregulation as a key contributor to immune dysfunction in PMM2-CDG. Importantly, our study identifies TNFR1 as a promising therapeutic target, suggesting that strategies aimed at modulating TNFR1 activity or restoring glycosylation homeostasis could provide new approaches for treatment development. This work advances our understanding of PMM2 -CDG immunopathology and opens opportunities for targeted therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1655354","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T05:32:30Z","timestamp":1758173550000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunopathology in PMM2-CDG: Defective glycosylation impact in the TNF\u03b1 -TNFR1 signalling pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Carlota","family":"Pascoal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Granjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeka","family":"Kodr\u00edkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Falc\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Teodoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Pakanov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Nem\u010dovi\u010d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Mucha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida","family":"Castro-Caldas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana R.","family":"Grosso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"dos Reis Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula A.","family":"Videira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04904-7","article-title":"An overview of the immune system","volume":"357","author":"Parkin","year":"2001","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2024.101900","article-title":"The role of sialoglycans in modulating dendritic cell function and tumour immunity","author":"Silva","year":"2024","journal-title":"Semin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s00262-024-03863-7","article-title":"New insights into the immunomodulatory potential of sialic acid on monocyte-derived dendritic cells","volume":"74","author":"Silva","year":"2024","journal-title":"Cancer Immunology Immunotherapy"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep08926","article-title":"Effects of N-glycosylation on protein conformation and dynamics: Protein Data Bank analysis and molecular dynamics simulation study","volume":"5","author":"Lee","year":"2015","journal-title":"Sci Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/FPED.2015.00054","article-title":"Glycans instructing immunity: the emerging role of altered glycosylation in clinical immunology","volume":"3","author":"Lyons","year":"2015","journal-title":"Front Pediatr"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.70011","article-title":"The therapeutic future for congenital disorders of glycosylation","volume":"48","author":"Muffels","year":"2025","journal-title":"J Inherit Metab Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJMG.2017.10.012","article-title":"Congenital disorders of glycosylation (CDG): Quo vadis","volume":"61","author":"P\u00e9anne","year":"2018","journal-title":"Eur J Med Genet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1002\/JIMD.12126","article-title":"CDG and immune response: From bedside to bench and back","volume":"43","author":"Pascoal","year":"2020","journal-title":"J Inherit Metab Dis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1016\/J.JACI.2019.11.016","article-title":"Defining a new immune deficiency syndrome: MAN2B2-CDG","volume":"145","author":"Verheijen","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2024.1350101","article-title":"Revisiting the immunopathology of congenital disorders of glycosylation: an updated review","volume":"15","author":"Pascoal","year":"2024","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/S10545-016-9954-9","article-title":"Immunological aspects of congenital disorders of glycosylation (CDG): a review","volume":"39","author":"Monticelli","year":"2016","journal-title":"J Inherit Metab Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198002000-00117","article-title":"Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG-deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome","volume":"14","author":"Jaeken","year":"1980","journal-title":"Pediatr Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/JIMD.12024","article-title":"International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up","volume":"42","author":"Altassan","year":"2019","journal-title":"J Inherit Metab Dis"},{"key":"B14","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1186\/s13023-024-03389-2","article-title":"Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community","volume":"19","author":"Granjo","year":"2024","journal-title":"Orphanet J Rare Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS19020619","article-title":"Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy","volume":"19","author":"Izquierdo-Serra","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/JMEDGENET-2017-104903","article-title":"Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature","volume":"54","author":"Schiff","year":"2017","journal-title":"J Med Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1007\/S10545-006-0275-2","article-title":"Recurrent infections and immunological dysfunction in congenital disorder of glycosylation Ia (CDG Ia)","volume":"29","author":"Blank","year":"2006","journal-title":"J Inherit Metab Dis"},{"key":"B18","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1186\/s13023-022-02551-y","article-title":"Patient reported outcomes for phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG): listening to what matters for the patients and health professionals","volume":"17","author":"Pascoal","year":"2022","journal-title":"Orphanet J Rare Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072092","article-title":"New insights into immunological involvement in congenital disorders of glycosylation (CDG) from a people-centric approach","volume":"9","author":"Francisco","year":"2020","journal-title":"J Clin Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/S12024-009-9108-6","article-title":"Retinal hemorrhages associated with meningitis in a child with a congenital disorder of glycosylation","volume":"5","author":"Ong","year":"2009","journal-title":"Forensic Sci Med Pathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0158863","article-title":"Natural killer cell receptors and cytotoxic activity in phosphomannomutase 2 deficiency (PMM2-CDG)","volume":"11","author":"Garc\u00eda-L\u00f3pez","year":"2016","journal-title":"PloS One"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/S13023-014-0207-4","article-title":"29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype","volume":"9","author":"Monin","year":"2014","journal-title":"Orphanet J Rare Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1136\/JMG.2006.044735","article-title":"Congenital disorder of glycosylation type Ia presenting with hydrops fetalis","volume":"44","author":"Van De Kamp","year":"2007","journal-title":"J Med Genet"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/JMG.38.1.14","article-title":"A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases","volume":"38","author":"De Lonlay","year":"2001","journal-title":"J Med Genet"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/J.YMGME.2008.05.005","article-title":"Pericardial and abdominal fluid accumulation in congenital disorder of glycosylation type Ia","volume":"94","author":"Truin","year":"2008","journal-title":"Mol Genet Metab"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1350101","article-title":"Revisiting the immunopathology of congenital disorders of glycosylation: an updated review","volume":"15","author":"Pascoal","year":"2024","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167163","article-title":"Transcriptomic analysis identifies dysregulated pathways and therapeutic targets in PMM2-CDG","volume":"1870","author":"Gallego","year":"2024","journal-title":"Biochim Biophys Acta (BBA) - Mol Basis Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-170","article-title":"GPI-anchor and GPI-anchored protein expression in PMM2-CDG patients","volume":"8","author":"De La Morena-Barrio","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"B29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/ncb1086","article-title":"A physical and functional map of the human TNF-\u03b1\/NF-\u03baB signal transduction pathway","volume":"6","author":"Bouwmeester","year":"2004","journal-title":"Nat Cell Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2020.585880\/BIBTEX","article-title":"Tumor necrosis factor receptors: pleiotropic signaling complexes and their differential effects","volume":"11","author":"Gough","year":"2020","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nri3834","article-title":"Regulation of tumour necrosis factor signalling: live or let die","volume":"15","author":"Brenner","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/SJ.BJP.0704549","article-title":"TNF ligands and receptors\u2009\u2013\u2009a matter of life and death","volume":"135","author":"MacEwan","year":"2002","journal-title":"Br J Pharmacol"},{"key":"B33","article-title":"TNFRSF1A - Tumor necrosis factor receptor superfamily member 1A - Homo sapiens (Human)","year":"","journal-title":"UniProtKB"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-015-9619-1","article-title":"The role of N-Glycan modification of TNFR1 in inflammatory microglia activation","volume":"32","author":"Han","year":"2015","journal-title":"Glycoconj J"},{"key":"B35","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s13023-025-03669-5","article-title":"A comprehensive update of genotype\u2013phenotype correlations in PMM2-CDG: insights from molecular and structural analyses","volume":"20","author":"Oliveira","year":"2025","journal-title":"Orphanet J Rare Dis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msh010","article-title":"Mammalian housekeeping genes evolve more slowly than tissue-specific genes","volume":"21","author":"Zhang","year":"2004","journal-title":"Mol Biol Evol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/978-1-4939-7704-8_5","article-title":"CSF N-glycomics using MALDI MS techniques in alzheimer\u2019s disease","author":"Palmigiano","year":"2018"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1021\/pr7008252","article-title":"GlycoWorkbench: A tool for the computer-assisted annotation of mass spectra of glycans","volume":"7","author":"Ceroni","year":"2008","journal-title":"J Proteome Res"},{"key":"B39","unstructured":"Babraham Bioinformatics - FastQC A Quality Control tool for High Throughput Sequence Data"},{"key":"B40","unstructured":"BBDuk Guide"},{"key":"B41","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/BIOINFORMATICS\/BTS635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"B43","doi-asserted-by":"publisher","first-page":"7866","DOI":"10.1038\/ncomms8866","article-title":"A draft network of ligand\u2013receptor-mediated multicellular signalling in human","volume":"6","author":"Ramilowski","year":"2015","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/70487","article-title":"Analysis of human transcriptomes","volume":"23","author":"Velculescu","year":"1999","journal-title":"Nat Genet"},{"key":"B45","unstructured":"R: A language and environment for statistical computing\n          \n          2022"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene Suite for gene list enrichment analysis and candidate gene prioritization","volume":"37","author":"Chen","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1031","article-title":"The reactome pathway knowledgebase","author":"Jassal","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B48","unstructured":"PGranjo\/immunological-involvement-in-PMM2-CDG"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1086\/301763","article-title":"Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A","volume":"62","author":"Matthijs","year":"1998","journal-title":"Am J Hum Genet"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.00055","article-title":"Biological and technical challenges in unraveling the role of N-glycans in immune receptor regulation","volume":"8","author":"de Haas","year":"2020","journal-title":"Front Chem"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1403","article-title":"Adaptive immune activation: glycosylation does matter","volume":"9","author":"Wolfert","year":"2013","journal-title":"Nat Chem Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12071446","article-title":"Glycosylation and its role in immune checkpoint proteins: from molecular mechanisms to clinical implications","volume":"12","author":"Liu","year":"2024","journal-title":"Biomedicines"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2007.98","article-title":"The transmembrane domain of TACE regulates protein ectodomain shedding","volume":"17","author":"Li","year":"2007","journal-title":"Cell Res"},{"key":"B54","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ab.2013.12.018","article-title":"Glycosylation of a disintegrin and metalloprotease 17 affects its activity and inhibition","volume":"449","author":"Chavaroche","year":"2014","journal-title":"Anal Biochem"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040435","article-title":"Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases","volume":"200","author":"Xanthoulea","year":"2004","journal-title":"J Exp Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00302.2004","article-title":"Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury","volume":"288","author":"Parsons","year":"2005","journal-title":"Am J Physiology-Lung Cell Mol Physiol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx493.P6229","article-title":"P6229TACE gene expression and soluble receptors TNFRI and TNFRII levels identifies very high risk cardiovascular patients","volume":"38","author":"Chemaly","year":"2017","journal-title":"Eur Heart J"},{"key":"B58","doi-asserted-by":"publisher","first-page":"29","DOI":"10.2302\/kjm.2012-0003-RE","article-title":"A brief history of tumor necrosis factor \u03b1 \u2013 converting enzyme: an overview of ectodomain shedding","volume":"62","author":"Horiuchi","year":"2013","journal-title":"Keio J Med"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02348.x","article-title":"Tumour necrosis factor- \u03b1 converting enzyme (TACE) activity in human colonic epithelial cells","volume":"135","author":"Kirkegaard","year":"2003","journal-title":"Clin Exp Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.365171","article-title":"A role for cGMP in inducible nitric-oxide synthase (iNOS)-induced tumor necrosis factor (TNF) \u03b1-converting enzyme (TACE\/ADAM17) activation, translocation, and TNF receptor 1 (TNFR1) shedding in hepatocytes","volume":"287","author":"Chanthaphavong","year":"2012","journal-title":"J Biol Chem"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/2395269","article-title":"Tumor necrosis factor-\u03b1: the next marker of stroke","volume":"2022","author":"Xue","year":"2022","journal-title":"Dis Markers"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2007.07.008","article-title":"Tumor necrosis factor and stroke: Role of the blood\u2013brain barrier","volume":"83","author":"Pan","year":"2007","journal-title":"Prog Neurobiol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020619","article-title":"Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy","volume":"19","author":"Izquierdo-Serra","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2022.893365","article-title":"N-glycosylation and inflammation; the not-so-sweet relation","volume":"13","author":"Radovani","year":"2022","journal-title":"Front Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS5040043","article-title":"Role of cytokine-induced glycosylation changes in regulating cell interactions and cell signaling in inflammatory diseases and cancer","volume":"5","author":"Dewald","year":"2016","journal-title":"Cells"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1021\/PR500146Y","article-title":"The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions","volume":"13","author":"McCarthy","year":"2014","journal-title":"J Proteome Res"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1074\/MCP.M115.054122","article-title":"Glycomic characterization of induced pluripotent stem cells derived from a patient suffering from phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG)","volume":"15","author":"Thiesler","year":"2016","journal-title":"Mol Cell Proteomics"},{"key":"B68","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/J.BBRC.2014.06.021","article-title":"Mannose metabolism: more than meets the eye","volume":"453","author":"Sharma","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM-2022-0641","article-title":"Unique clinical presentations and follow-up outcomes from experience with congenital disorders of glycosylation: PMM2-PGM1-DPAGT1-MPI-POMT2-B3GALNT2-DPM1-SRD5A3-CDG","volume":"36","author":"Yoldas Celik","year":"2023","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/S41580-020-0255-7","article-title":"ERK signalling: a master regulator of cell behaviour, life and fate","volume":"21","author":"Lavoie","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M412837200","article-title":"Tpl2\/cot signals activate ERK, JNK, and NF-kappaB in a cell-type and stimulus-specific manner","volume":"280","author":"Dasi","year":"2005","journal-title":"J Biol Chem"},{"key":"B72","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/NRRHEUM.2017.83","article-title":"The role of IL-6 in host defence against infections: immunobiology and clinical implications","volume":"13","author":"Rose-John","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.4049\/JIMMUNOL.0990015","article-title":"The unexpected pleiotropic activities of RANTES","volume":"182","author":"Levy","year":"2009","journal-title":"J Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1093\/GLYCOB\/CWU006","article-title":"N-glycosylation deficiency reduces ICAM-1 induction and impairs inflammatory response","volume":"24","author":"He","year":"2014","journal-title":"Glycobiology"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00116-1","article-title":"Signal transduction by the JNK group of MAP kinases","volume":"103","author":"Davis","year":"2000","journal-title":"Cell"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1038\/NI.1640","article-title":"p38\u03b1 MAP kinase serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression","volume":"9","author":"Kim","year":"2008","journal-title":"Nat Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELLSIG.2009.02.006","article-title":"ERK1\/2, but not ERK5, is necessary and sufficient for phosphorylation and activation of c-Fos","volume":"21","author":"Gilley","year":"2009","journal-title":"Cell Signal"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBAMCR.2010.12.012","article-title":"The MAPK cascades: Signaling components, nuclear roles and mechanisms of nuclear translocation","volume":"1813","author":"Plotnikov","year":"2011","journal-title":"Biochim Biophys Acta (BBA) - Mol Cell Res"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/SJ.ONC.1204380","article-title":"Function and regulation of AP-1 subunits in skin physiology and pathology","volume":"20","author":"Angel","year":"2001","journal-title":"Oncogene"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.10.7101","article-title":"MAPK p38 Regulates Transcriptional Activity of NF-\u03baB in Primary Human Astrocytes via Acetylation of p65","volume":"179","author":"Saha","year":"2007","journal-title":"J Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2025.107057","article-title":"Unraveling the biological potential of skin fibroblast: responses to TNF-\u03b1, highlighting intracellular signaling pathways and secretome","volume":"276","author":"Pascoal","year":"2025","journal-title":"Immunol Lett"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2025.109188","article-title":"Incidence and prevalence of phosphomannomutase 2-congenital disorder of glycosylation: Past, present, and future","volume":"146","author":"Edmondson","year":"2025","journal-title":"Mol Genet Metab"},{"key":"B83","unstructured":"London\n          Guideline on clinical trials in small populations\n          \n          2006"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1655354\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T05:32:33Z","timestamp":1758173553000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1655354\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":83,"alternative-id":["10.3389\/fimmu.2025.1655354"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1655354","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"article-number":"1655354"}}