{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:00:30Z","timestamp":1777356030823,"version":"3.51.4"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"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>Background<\/jats:title>\n                    <jats:p>\n                      Migraine, a prevalent and debilitating neurovascular disorder, frequently co-occurs with functional dyspepsia. Emerging evidence suggests that\n                      <jats:italic>Helicobacter pylori (H. pylori)<\/jats:italic>\n                      infection may contribute to both conditions via neuroimmune pathways, though the molecular basis for this association has yet to be fully elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -related datasets from GEO were analyzed to identify differentially expressed genes (DEGs), followed by functional enrichment analyses including GO, KEGG, GSEA, and GSVA. Immune infiltration patterns were assessed, and CGRP-related hub genes were identified using machine learning approaches. The relationship between these hub genes and immune cell infiltration\u2014particularly M1 macrophage polarization\u2014was explored, and the interaction between CALCA and PNOC was analyzed by correlation analysis and protein-protein interaction networks. Experimental validation was performed using RT-qPCR in\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -infected THP-1 macrophages and SH-SY5Y neuronal cells, along with loss- and gain-of-function experiments to investigate regulatory relationships.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptomic analysis of\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -infected patients identified 683 differentially expressed genes enriched in immune and inflammatory pathways. Immune profiling further revealed prominent M1 macrophage polarization with increased \u03b3\u03b4T cells and B lymphocytes. Among the DEGs, four CGRP-related hub genes (PNOC, ICAM1, MMP9, and NFE2L1) were identified and found upregulated in\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -infected macrophages. Correlation analyses showed PNOC, ICAM1, and MMP9 positively associated with M1 macrophages and their canonical markers, with knockdown of each gene attenuating M1 marker expression. In contrast, NFE2L1 showed no significant correlation, yet its knockdown increased M1 marker expression. Among the hub genes, only PNOC correlated positively with CALCA; both were upregulated in\n                      <jats:italic>H. pylori<\/jats:italic>\n                      -infected neuronal cells. Notably, PNOC knockdown in macrophages reduced CALCA expression in co-cultured neurons, while overexpression had the opposite effect, suggesting macrophage-derived PNOC may regulate neuronal CGRP expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection may promote migraine and functional dyspepsia through gastric inflammation and neuroimmune signaling. This process involves four key genes\u2014PNOC, ICAM1, MMP9, and NFE2L1\u2014that regulate M1 macrophage polarization and pro-inflammatory responses. Among them, PNOC appears to link gastric inflammation to neurological symptoms by modulating neuronal CGRP. Together, these findings point to gut-brain axis involvement in this comorbidity and may inform future therapies targeting\n                      <jats:italic>H. pylori<\/jats:italic>\n                      eradication and CGRP-related pathways.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1684555","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:30:12Z","timestamp":1777354212000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Screening and functional validation of key genes in Helicobacter Pylori-induced macrophage M1 polarization: role in migraine-associated functional dyspepsia"],"prefix":"10.3389","volume":"17","author":[{"given":"Nengjin","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]},{"name":"Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaile","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]},{"name":"Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianli","family":"Gou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]},{"name":"Department of Gastroenterology, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panpan","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]},{"name":"Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"Shi","sequence":"additional","affiliation":[{"name":"School Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Xiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]},{"name":"Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shenglin","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihan","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujuan","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]},{"name":"Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/0333102413485658","article-title":"The international classification of headache disorders, 3rd edition","volume":"38","year":"2018","journal-title":"Cephalalgia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s10194-024-01798-z","article-title":"Global, regional, and national burden and trends of migraine among women of childbearing age from 1990 to 2021: insights from the Global Burden of Disease Study 2021","volume":"25","author":"Cen","year":"2024","journal-title":"J Headache Pain"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115133","article-title":"CCL2 activates NLRP3 inflammasomes to regulate microglial phenotype transformation to promote central sensitisation in chronic migraine","volume":"162","author":"Wang","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.5381800","article-title":"Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021","volume":"23","year":"2024","journal-title":"Lancet Neurol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419857596","article-title":"Prevalence and pathophysiology of post-prandial migraine in patients with functional dyspepsia","volume":"39","author":"Di Stefano","year":"2019","journal-title":"Cephalalgia"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30469-4","article-title":"Functional dyspepsia","volume":"396","author":"Ford","year":"2020","journal-title":"Lancet"},{"key":"B7","article-title":"Functional dyspepsia","volume-title":"StatPearls","author":"Francis","year":"2025"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.81","article-title":"Functional dyspepsia","volume":"3","author":"Enck","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.2018.0222","article-title":"The diagnosis and treatment of functional dyspepsia","volume":"115","author":"Madisch","year":"2018","journal-title":"Dtsch Arztebl Int"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.5056\/jnm18068","article-title":"Prevalence and risk factors of functional dyspepsia in health check-up population: a nationwide multicenter prospective study","volume":"24","author":"Kim","year":"2018","journal-title":"J Neurogastroenterol Motil"},{"key":"B11","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1136\/egastro-2024-100119","article-title":"Functional dyspepsia and gastroparesis: are they distinct disorders, a spectrum of diseases or one disease","volume":"3","author":"Egboh","year":"2025","journal-title":"eGastroenterology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/head.14099","article-title":"A link between gastrointestinal disorders and migraine: insights into the gut-brain connection","volume":"61","author":"Aurora","year":"2021","journal-title":"Headache"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i36.8149","article-title":"Gastrointestinal disorders associated with migraine: a comprehensive review","volume":"22","author":"Camara-Lemarroy","year":"2016","journal-title":"World J Gastroenterol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-823357-3.00024-0","article-title":"CGRP monoclonal antibodies and CGRP receptor antagonists (Gepants) in migraine prevention","volume":"199","author":"Caronna","year":"2024","journal-title":"Handb Clin Neurol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00059.2021","article-title":"CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond","volume":"103","author":"Russo","year":"2023","journal-title":"Physiol Rev"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41572-021-00328-4","article-title":"Migraine","volume":"8","author":"Ferrari","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-324674","article-title":"Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effects","volume":"92","author":"Ray","year":"2021","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105840","article-title":"The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders","volume":"172","author":"Socala","year":"2021","journal-title":"Pharmacol Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/978-1-4939-0897-4_9","article-title":"Neuropeptides and the microbiota-gut-brain axis","volume":"817","author":"Holzer","year":"2014","journal-title":"Adv Exp Med Biol"},{"key":"B20","doi-asserted-by":"publisher","article-title":"Helicobacter pylori: background document for the WHO guidelines for drinking-water quality and the WHO guidelines on sanitation and health","year":"2025","DOI":"10.2471\/b09230"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i40.14965","article-title":"Association between Helicobacter pylori infection and migraine: a meta-analysis","volume":"20","author":"Su","year":"2014","journal-title":"World J Gastroenterol"},{"key":"B22","article-title":"The effect of Helicobacter pylori eradication on migraine: a randomized, double blind, controlled trial","volume":"15","author":"Faraji","year":"2012","journal-title":"Pain Physician"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i12.3486","article-title":"Helicobacter pylori eradication therapy for functional dyspepsia: systematic review and meta-analysis","volume":"22","author":"Du","year":"2016","journal-title":"World J Gastroenterol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.938608","article-title":"Relationship between Helicobacter pylori infection and gastrointestinal microecology","volume":"12","author":"Xu","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s10194-020-1078-9","article-title":"Gut-brain axis and migraine headache: a comprehensive review","volume":"21","author":"Arzani","year":"2020","journal-title":"J Headache Pain"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06150-w","article-title":"Single-cell profiling reveals a reduced epithelial defense system, decreased immune responses and the immune regulatory roles of different fibroblast subpopulations in chronic atrophic gastritis","volume":"23","author":"Lin","year":"2025","journal-title":"J Transl Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00187.2012","article-title":"H. pylori acutely inhibits gastric secretion by activating CGRP sensory neurons coupled to stimulation of somatostatin and inhibition of histamine secretion","volume":"304","author":"Zaki","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2024.189139","article-title":"Helicobacter pylori triggers inflammation and oncogenic transformation by perturbing the immune microenvironment","volume":"1879","author":"Wang","year":"2024","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.946832","article-title":"Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis","volume":"13","author":"Wen","year":"2022","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in immunoregulation and therapeutics","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B31","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/mi.2016.60","article-title":"TRPM2 ion channels regulate macrophage polarization and gastric inflammation during Helicobacter pylori infection","volume":"10","author":"Beceiro","year":"2017","journal-title":"Mucosal Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/1040841x.2024.2366944","article-title":"Macrophage biology in the pathogenesis of Helicobacter pylori infection","volume":"51","author":"Fei","year":"2025","journal-title":"Crit Rev Microbiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12910","article-title":"Implications of macrophage polarization in autoimmunity","volume":"154","author":"Funes","year":"2018","journal-title":"Immunology"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, mechanisms, and significance of macrophage plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu Rev Pathol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.conb.2019.11.006","article-title":"Regulation of pain by neuro-immune interactions between macrophages and nociceptor sensory neurons","volume":"62","author":"Chen","year":"2020","journal-title":"Curr Opin Neurobiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0368-23.2023","article-title":"Meningeal P2X7 signaling mediates migraine-related intracranial mechanical hypersensitivity","volume":"43","author":"Zhao","year":"2023","journal-title":"J Neurosci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001789","article-title":"Celecoxib reduces cortical spreading depression-induced macrophage activation and dilatation of dural but not pial arteries in rodents: implications for mechanism of action in terminating migraine attacks","volume":"161","author":"Schain","year":"2020","journal-title":"Pain"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.01.012","article-title":"Functional dyspepsia: eosinophils, macrophages, and the postinfectious state","volume":"140","author":"Craig","year":"2011","journal-title":"Gastroenterology"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.831761","article-title":"Immune activation in functional dyspepsia: bystander becoming the suspect","volume":"16","author":"Ceulemans","year":"2022","journal-title":"Front Neurosci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab024","article-title":"Targeting immune cell metabolism in the treatment of inflammatory bowel disease","volume":"27","author":"Zaiatz Bittencourt","year":"2021","journal-title":"Inflammation Bowel Dis"},{"key":"B42","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1371\/journal.pone.0171139","article-title":"Silymarin suppresses basal and stimulus-induced activation, exhaustion, differentiation, and inflammatory markers in primary human immune cells","volume":"12","author":"Lovelace","year":"2017","journal-title":"PloS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s44385-025-00010-4","article-title":"Inflammation: a matter of immune cell life and death","volume":"2","author":"Bender","year":"2025","journal-title":"NPJ BioMed Innov"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.944791","article-title":"Immunologic aspects of migraine: a review of literature","volume":"13","author":"Salahi","year":"2022","journal-title":"Front Neurol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1007\/s11481-025-10197-3","article-title":"Revisiting migraine pathophysiology: from neurons to immune cells through lens of immune regulatory pathways","volume":"20","author":"Subalakshmi","year":"2025","journal-title":"J Neuroimmune Pharmacol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02229-5","article-title":"Headache and immunological\/autoimmune disorders: a comprehensive review of available epidemiological evidence with insights on potential underlying mechanisms","volume":"18","author":"Biscetti","year":"2021","journal-title":"J Neuroinflamm"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.647209","article-title":"PNOC expressed by B cells in cholangiocarcinoma was survival related and LAIR2 could be a T cell exhaustion biomarker in tumor microenvironment: characterization of immune microenvironment combining single-cell and bulk sequencing technology","volume":"12","author":"Chen","year":"2021","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1177\/20584601251330563","article-title":"MMP-9 metalloproteinase and its regulator are not associated with mid-term CT residual abnormalities in patients with COVID-19 pneumonia","volume":"14","author":"Mattone","year":"2025","journal-title":"Acta Radiol Open"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/cells13181554","article-title":"Intercellular adhesion molecule 1 (ICAM-1): an inflammatory regulator with potential implications in ferroptosis and Parkinson's disease","volume":"13","author":"Miller","year":"2024","journal-title":"Cells"},{"key":"B50","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.freeradbiomed.2018.01.022","article-title":"Silencing of long isoforms of nuclear factor erythroid 2 like 1 primes macrophages towards M1 polarization","volume":"117","author":"Wang","year":"2018","journal-title":"Free Radic Biol Med"},{"key":"B51","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12964-024-02017-7","article-title":"Helicobacter pylori infection promotes M1 macrophage polarization and gastric inflammation by activation of NLRP3 inflammasome via TNF\/TNFR1 axis","volume":"23","author":"Fei","year":"2025","journal-title":"Cell Commun Signal"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.14740\/gr1636","article-title":"Effects of Helicobacter pylori infection on the prognosis of chronic atrophic gastritis by inducing the macrophage polarization","volume":"16","author":"Zhao","year":"2023","journal-title":"Gastroenterol Res"},{"key":"B53","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1093\/abt\/tbad029","article-title":"CD80-Fc fusion protein as a potential cancer immunotherapy strategy","volume":"7","author":"Wang","year":"2024","journal-title":"Antib Ther"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1352946","article-title":"Macrophage polarization: an important role in inflammatory diseases","volume":"15","author":"Luo","year":"2024","journal-title":"Front Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/981328","article-title":"Helicobacter pylori and T helper cells: mechanisms of immune escape and tolerance","volume":"2015","author":"Larussa","year":"2015","journal-title":"J Immunol Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1078\/1438-4221-00165","article-title":"The neutrophil-activating protein of Helicobacter pylori","volume":"291","author":"Dundon","year":"2002","journal-title":"Int J Med Microbiol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12405","article-title":"Pathogenesis of Helicobacter pylori infection","volume":"22","author":"Camilo","year":"2017","journal-title":"Helicobacter"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2017.11.007","article-title":"CXCL9, CXCL10, CXCL11\/CXCR3 axis for immune activation - a target for novel cancer therapy","volume":"63","author":"Tokunaga","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"B59","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3390\/gidisord7010006","article-title":"The role of the immune response to Helicobacter pylori antigens and its relevance in gastric disorders","volume":"7","author":"Santacroce","year":"2025","journal-title":"Gastrointestinal Disord"},{"key":"B60","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1159\/000508330","article-title":"The protective effects of Helicobacter pylori infection on allergic asthma","volume":"182","author":"Zuo","year":"2021","journal-title":"Int Arch Allergy Immunol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3390\/antibiotics12020191","article-title":"Helicobacter pylori infection: current status and future prospects on diagnostic, therapeutic and control challenges","volume":"12","author":"Elbehiry","year":"2023","journal-title":"Antibiotics (Basel)"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102399","article-title":"Research progress on Helicobacter pylori infection related neurological diseases","volume":"99","author":"Wang","year":"2024","journal-title":"Ageing Res Rev"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12454","article-title":"Review: impact of Helicobacter pylori on Alzheimer's disease: what do we know so far","volume":"23","author":"Doulberis","year":"2018","journal-title":"Helicobacter"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/hel.12165","article-title":"Epidemiology of Helicobacter pylori infection","volume":"19","author":"Eusebi","year":"2014","journal-title":"Helicobacter"},{"key":"B65","article-title":"An increased number of gamma\/delta T-cells and gastric epithelial cell expression of the groEL stress-protein homologue in Helicobacter pylori-associated chronic gastritis of the antrum","volume":"86","author":"Engstrand","year":"1991","journal-title":"Am J Gastroenterol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13045-024-01654-2","article-title":"Helicobacter pylori and gastric cancer: mechanisms and new perspectives","volume":"18","author":"Duan","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1159\/000368232","article-title":"Helicobacter pylori inhibits dendritic cell maturation via interleukin-10-mediated activation of the signal transducer and activator of transcription 3 pathway","volume":"7","author":"Rizzuti","year":"2015","journal-title":"J Innate Immun"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.11817\/j.issn.1672-7347.2024.240017","article-title":"Role of M1\/M2 macrophages in pain modulation","volume":"49","author":"Zhu","year":"2024","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1126\/science.2994212","article-title":"Expression in brain of a messenger RNA encoding a novel neuropeptide homologous to calcitonin gene-related peptide","volume":"229","author":"Amara","year":"1985","journal-title":"Science"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/s0196-9781(00)00247-3","article-title":"Nocistatin: a novel neuropeptide encoded by the gene for the nociceptin\/orphanin FQ precursor","volume":"21","author":"Okuda-Ashitaka","year":"2000","journal-title":"Peptides"},{"key":"B71","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1371\/journal.pone.0074138","article-title":"Inflammatory mediators influence the expression of nociceptin and its receptor in human whole blood cultures","volume":"8","author":"Zhang","year":"2013","journal-title":"PloS One"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/bs.vh.2014.11.003","article-title":"Nociceptin\/orphanin FQ-NOP receptor system in inflammatory and immune-mediated diseases","volume":"97","author":"Gavioli","year":"2015","journal-title":"Vitam Horm"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810546","article-title":"The role of matrix metalloproteinase in inflammation with a focus on infectious diseases","volume":"23","author":"Lee","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25189-z","article-title":"ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer","volume":"12","author":"Taftaf","year":"2021","journal-title":"Nat Commun"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202302176r","article-title":"Systematic pan-cancer analysis insights into ICAM1 as an immunological and prognostic biomarker","volume":"38","author":"Yang","year":"2024","journal-title":"FASEB J"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.3023","article-title":"Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells","volume":"96","author":"Luksch","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01164.x","article-title":"Expression of HLA-DR, costimulatory molecules B7-1, B7-2, intercellular adhesion molecule-1 (ICAM-1) and Fas ligand (FasL) on gastric epithelial cells in Helicobacter pylori gastritis; influence of H. pylori eradication","volume":"119","author":"Archimandritis","year":"2000","journal-title":"Clin Exp Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.gene.2016.03.002","article-title":"Nuclear factor erythroid-2 like 1 (NFE2L1): structure, function and regulation","volume":"584","author":"Kim","year":"2016","journal-title":"Gene"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11289","article-title":"Downregulation of miR-486-5p alleviates LPS-induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1","volume":"22","author":"Chang","year":"2020","journal-title":"Mol Med Rep"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1307319","article-title":"A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study","volume":"15","author":"Rushendran","year":"2024","journal-title":"Front Neurol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2021.06.002","article-title":"Helicobacter pylori promotes gastric cancer progression by upregulating semaphorin 5A expression via ERK\/MMP9 signaling","volume":"22","author":"Pan","year":"2021","journal-title":"Mol Ther Oncolytics"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050130","article-title":"Inhibition of intercellular adhesion molecule-1 (ICAM-1), soluble ICAM-1 and interleukin-4 by nitric oxide expression in migraine patients","volume":"75","author":"Martelletti","year":"1997","journal-title":"J Mol Med (Berl)"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.07.030","article-title":"Associations of a polymorphism in the intercellular adhesion molecule-1 (ICAM1) gene and ICAM1 serum levels with migraine in a Chinese Han population","volume":"345","author":"He","year":"2014","journal-title":"J Neurol Sci"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.2174\/1871527317666171213154749","article-title":"The combined effects of omega -3 fatty acids and nano-curcumin supplementation on intercellular adhesion molecule-1 (ICAM-1) gene expression and serum levels in migraine patients","volume":"16","author":"Soveyd","year":"2018","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2008.01228.x","article-title":"Serum concentrations of s100b and NSE in migraine","volume":"49","author":"Teepker","year":"2009","journal-title":"Headache"},{"key":"B86","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1111\/ane.13365","article-title":"S100B and neuron-specific enolase levels in episodic and chronic migraine","volume":"143","author":"Gonen","year":"2021","journal-title":"Acta Neurol Scand"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1684555\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:30:15Z","timestamp":1777354215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1684555\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":86,"alternative-id":["10.3389\/fimmu.2026.1684555"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1684555","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"article-number":"1684555"}}