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dc.contributor.authorCook, L
dc.contributor.authorLisko, DJ
dc.contributor.authorWong, MQ
dc.contributor.authorGarcia, R
dc.contributor.authorHimmel, ME
dc.contributor.authorSeidman, EG
dc.contributor.authorBressler, B
dc.contributor.authorLevings, MK
dc.contributor.authorSteiner, TS
dc.date.accessioned2020-11-17T04:20:11Z
dc.date.available2020-11-17T04:20:11Z
dc.date.issued2020-01-01
dc.identifierpii: S2352-345X(19)30167-5
dc.identifier.citationCook, L., Lisko, D. J., Wong, M. Q., Garcia, R., Himmel, M. E., Seidman, E. G., Bressler, B., Levings, M. K. & Steiner, T. S. (2020). Analysis of Flagellin Specific Adaptive Immnunity Reveals Links to Dysbioss in Patients With Inflammatory Bowel Disease. CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY, 9 (3), pp.485-506. https://doi.org/10.1016/j.jcmgh.2019.11.012.
dc.identifier.issn2352-345X
dc.identifier.urihttp://hdl.handle.net/11343/251776
dc.description.abstractBACKGROUND & AIMS: Bacterial flagellin is an important antigen in inflammatory bowel disease, but the role of flagellin-specific CD4+ T cells in disease pathogenesis remains unclear. Also unknown is how changes in intestinal microbiome intersect with those in microbiota-specific CD4+ T cells. We aimed to quantify and characterize flagellin-specific CD4+ T cells in Crohn's disease (CD) and ulcerative colitis (UC) patients and study their relationship with intestinal microbiome diversity. METHODS: Blood was collected from 3 cohorts that included CD patients, UC patients, and healthy controls. Flow cytometry analyzed CD4+ T cells specific for Lachnospiraceae-derived A4-Fla2 and Escherichia coli H18 FliC flagellins, or control vaccine antigens. Serum antiflagellin IgG and IgA antibodies were detected by enzyme-linked immunosorbent assay and stool samples were collected and subjected to 16S ribosomal DNA sequencing. RESULTS: Compared with healthy controls, CD and UC patients had lower frequencies of vaccine-antigen-specific CD4+ T cells and, as a proportion of vaccine-specific cells, higher frequencies of flagellin-specific CD4+ T cells. The proportion of flagellin-specific CD4+ T cells that were CXCR3negCCR4+CCR6+ Th17 cells was reduced in CD and UC patients, with increased proportions of CD39+, PD-1+, and integrin β7+ cells. Microbiome analysis showed differentially abundant bacterial species in patient groups that correlated with immune responses to flagellin. CONCLUSIONS: Both CD and UC patients have relative increases in the proportion of circulating Fla2-specific CD4+ T cells, which may be associated with changes in the intestinal microbiome. Evidence that the phenotype of these cells strongly correlate with disease severity provides insight into the potential roles of flagellin-specific CD4+ T cells in inflammatory bowel disease.
dc.languageEnglish
dc.publisherELSEVIER INC
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleAnalysis of Flagellin Specific Adaptive Immnunity Reveals Links to Dysbioss in Patients With Inflammatory Bowel Disease
dc.typeJournal Article
dc.identifier.doi10.1016/j.jcmgh.2019.11.012
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titleCellular and Molecular Gastroenterology and Hepatology
melbourne.source.volume9
melbourne.source.issue3
melbourne.source.pages485-506
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1478668
melbourne.contributor.authorCook, Laura
dc.identifier.eissn2352-345X
melbourne.accessrightsOpen Access


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