{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T17:10:03Z","timestamp":1793985003831,"version":"4.8.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Functional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 \u00b1 16.11, 19.84 \u00b1 15.51, <jats:italic>p<\/jats:italic>=0.038), central memory (23.75 \u00b1 18.97, 37.52 \u00b1 17.51, <jats:italic>p<\/jats:italic>=0.007) and effector memory (9.80\u00b110.50 vs 20.53\u00b114.15, <jats:italic>p<\/jats:italic>=0.001) populations. Th17 populations were also increased in the effector (31.74\u00b124.73 vs 45.57\u00b123.75, <jats:italic>p<\/jats:italic>=0.03) and effector memory (11.95\u00b18.42 vs 18.44\u00b115.63, <jats:italic>p<\/jats:italic>=0.027) subsets. Peripheral T cell populations were unchanged between FD and control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1051632","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T14:32:46Z","timestamp":1673015566000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia"],"prefix":"10.3389","volume":"13","author":[{"given":"Grace L.","family":"Burns","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica K.","family":"Bruce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra","family":"Minahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mathe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Fairlie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Naudin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prema M.","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D. E.","family":"Potter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudar Zand","family":"Irani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Bollipo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lay T.","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha A.","family":"Koloski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay C.","family":"Horvat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Veysey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Holtmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie M.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Talley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Keely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1053\/j.gastro.2016.02.032","article-title":"Functional gastrointestinal disorders: History, pathophysiology, clinical features and Rome IV","volume":"150","author":"Drossman","year":"2016","journal-title":"Gastroenterology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.07.053","article-title":"Analysis of postprandial symptom patterns in subgroups of patients with Rome III or Rome IV functional dyspepsia","volume":"18","author":"Carbone","year":"2020","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.03937.x","article-title":"Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia","volume":"29","author":"Walker","year":"2009","journal-title":"Aliment Pharmacol Ther"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.05.015","article-title":"Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study","volume":"5","author":"Talley","year":"2007","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04282.x","article-title":"Implications of eosinophilia in the normal duodenal biopsy - an association with allergy and functional dyspepsia","volume":"31","author":"Walker","year":"2010","journal-title":"Aliment Pharmacol Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303857","article-title":"Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia","volume":"63","author":"Vanheel","year":"2014","journal-title":"Gut"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12419","article-title":"Duodenal eosinophilia and early satiety in functional dyspepsia: Confirmation of a positive association in an Australian cohort","volume":"29","author":"Walker","year":"2014","journal-title":"J Gastroenterol Hepatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2015.02.001","article-title":"Quantitative evaluation of duodenal eosinophils and mast cells in adult patients with functional dyspepsia","volume":"19","author":"Wang","year":"2015","journal-title":"Ann Diagn Pathol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.512","article-title":"Small bowel homing T cells are associated with symptoms and delayed gastric emptying in functional dyspepsia","volume":"106","author":"Liebregts","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1038\/ctg.2017.12","article-title":"Endoscopy-guided evaluation of duodenal mucosal permeability in functional dyspepsia","volume":"8","author":"Ishigami","year":"2017","journal-title":"Clin Transl Gastroenterol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-019-5470-8","article-title":"The altered mucosal barrier function in the duodenum plays a role in the pathogenesis of functional dyspepsia","volume":"64","author":"Komori","year":"2019","journal-title":"Dig Dis Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01220.x","article-title":"Immune dysfunction in patients with functional gastrointestinal disorders","volume":"21","author":"Kindt","year":"2009","journal-title":"Neurogastroenterol Motil"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215093","article-title":"T Helper subset development: roles of instruction, selection, and transcription","volume":"109","author":"Farrar","year":"2002","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.immuni.2015.07.010","article-title":"Stop press: Eosinophils drafted to join the Th17 team","volume":"43","author":"Keely","year":"2015","journal-title":"Immunity"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41395-018-0377-0","article-title":"Evidence for local and systemic immune activation in functional dyspepsia and the irritable bowel syndrome: A systematic review","volume":"114","author":"Burns","year":"2019","journal-title":"Am J Gastroenterol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5343-6","article-title":"Overlap of irritable bowel syndrome and functional dyspepsia in the clinical setting: Prevalence and risk factors","volume":"64","author":"Von Wulffen","year":"2019","journal-title":"Digestive Dis Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2004.30040.x","article-title":"Impact of coexisting irritable bowel syndrome on symptoms and pathophysiological mechanisms in functional dyspepsia","volume":"99","author":"Corsetti","year":"2004","journal-title":"Am J Gastroenterol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12585","article-title":"Rome III functional dyspepsia subdivision in PDS and EPS: recognizing postprandial symptoms reduces overlap","volume":"27","author":"Carbone","year":"2015","journal-title":"Neurogastroenterol Motil"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.01.019","article-title":"Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia","volume":"101","author":"Bruce","year":"2022","journal-title":"Brain Behav Immun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(12)62169-7","article-title":"Assessment of functional gastrointestinal disease: the bowel disease questionnaire","volume":"65","author":"Talley","year":"1990","journal-title":"Mayo Clin Proc"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1999.00445.x","article-title":"Development of a new dyspepsia impact scale: the nepean dyspepsia index","volume":"13","author":"Talley","year":"1999","journal-title":"Aliment Pharmacol Ther"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.135","article-title":"Regulation of IL-12p40 by HIF controls Th1\/Th17 responses to prevent mucosal inflammation","volume":"10","author":"Marks","year":"2017","journal-title":"Mucosal Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44429-3","article-title":"Differential expression of CXCR3 and CCR6 on CD4+ T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome","volume":"9","author":"Silveira-Mattos","year":"2019","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/j.1600-065X.2010.01000.x","article-title":"Dissecting the human immunologic memory for pathogens","volume":"240","author":"Zielinski","year":"2011","journal-title":"Immunol Rev"},{"key":"B25","article-title":"Quantification of mucosal eosinophils for the histopathologic diagnosis of eosinophilic gastritis and duodenitis: A primer for practicing pathologists","volume":"46","author":"Turner","year":"2021","journal-title":"Am J Surg Pathol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00556-8","article-title":"CODEX multiplexed tissue imaging with DNA-conjugated antibodies","volume":"16","author":"Black","year":"2021","journal-title":"Nat Protoc"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"107523","DOI":"10.1016\/j.celrep.2020.107523","article-title":"CytoMAP: A spatial analysis toolbox reveals features of myeloid cell organization in lymphoid tissues","volume":"31","author":"Stoltzfus","year":"2020","journal-title":"Cell Rep"},{"key":"B29","doi-asserted-by":"publisher","first-page":"9086340","DOI":"10.1155\/2020\/9086340","article-title":"Patients with multiple functional gastrointestinal disorders (FGIDs) show increased illness severity: A cross-sectional study in a tertiary care FGID specialty clinic","author":"Berens","year":"2020","journal-title":"Gastroenterol Res Pract 2020"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03118-2","article-title":"Local immune response to food antigens drives meal-induced abdominal pain","volume":"590","author":"Aguilera-Lizarraga","year":"2021","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1053\/j.gastro.2019.03.046","article-title":"Many patients with irritable bowel syndrome have atypical food allergies not associated with immunoglobulin e","volume":"157","author":"Fritscher-Ravens","year":"2019","journal-title":"Gastroenterology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nri2735","article-title":"How are T(H)2-type immune responses initiated and amplified","volume":"10","author":"Paul","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i24.7349","article-title":"Effector and suppressor T cells in celiac disease","volume":"21","author":"Mazzarella","year":"2015","journal-title":"World J Gastroenterol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2018.11.015","article-title":"A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorders","volume":"105","author":"Kamali","year":"2019","journal-title":"Mol Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601373","article-title":"Inflammasome and fas-mediated IL-1beta contributes to Th17\/Th1 cell induction in pathogenic bacterial infection in vivo","volume":"199","author":"Uchiyama","year":"2017","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2019.1666002","article-title":"Role of IL-17 in asthma pathogenesis and its implications for the clinic","volume":"13","author":"Ramakrishnan","year":"2019","journal-title":"Expert Rev Respir Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/MCP.0000000000000536","article-title":"Unravelling the complexity of tissue inflammation in uncontrolled and severe asthma","volume":"25","author":"Erjefalt","year":"2019","journal-title":"Curr Opin Pulmonary Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15120","article-title":"Population based study: atopy and autoimmune diseases are associated with functional dyspepsia and irritable bowel syndrome, independent of psychological distress","volume":"49","author":"Koloski","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12903","article-title":"Increased prevalence of autoimmune diseases in functional gastrointestinal disorders: case-control study of 23471 primary care patients","volume":"40","author":"Ford","year":"2014","journal-title":"Aliment Pharmacol Ther"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2019.1596025","article-title":"Follow up on atopy and the gastrointestinal tract - a review of a common association 2018","volume":"13","author":"Walker","year":"2019","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.cell.2012.09.016","article-title":"A validated regulatory network for Th17 cell specification","volume":"151","author":"Ciofani","year":"2012","journal-title":"Cell"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12846","article-title":"The overlap of atopy and functional gastrointestinal disorders among 23,471 patients in primary care","volume":"40","author":"Jones","year":"2014","journal-title":"Aliment Pharmacol Ther"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.5056\/jnm16214","article-title":"What is new in Rome IV","volume":"23","author":"Schmulson","year":"2017","journal-title":"J Neurogastroenterol Motil"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00639","article-title":"The Treg\/Th17 axis: A dynamic balance regulated by the gut microbiome","volume":"6","author":"Omenetti","year":"2015","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1051632\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T14:32:50Z","timestamp":1673015570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1051632\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2022.1051632"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1051632","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]},"article-number":"1051632"}}