TY  - JOUR
AU  - Cook, L
AU  - Lisko, DJ
AU  - Wong, MQ
AU  - Garcia, R
AU  - Himmel, ME
AU  - Seidman, EG
AU  - Bressler, B
AU  - Levings, MK
AU  - Steiner, TS
Y2  - 2020/11/17
Y1  - 2020/01/01
SN  - 2352-345X
UR  - http://hdl.handle.net/11343/251776
AB  - BACKGROUND & 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.
LA  - English
PB  - ELSEVIER INC
T1  - Analysis of Flagellin Specific Adaptive Immnunity Reveals Links to Dysbioss in Patients With Inflammatory Bowel Disease
DO  - 10.1016/j.jcmgh.2019.11.012
IS  - Cellular and Molecular Gastroenterology and Hepatology
VL  - 9
IS  - 3
SP  - 485-506
L1  - /bitstream/handle/11343/251776/PMC7036547.pdf?sequence=1&isAllowed=y
ER  -