TY - JOUR
T1 - Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota
AU - Regner, Emilie H.
AU - Ohri, Neha
AU - Stahly, Andrew
AU - Gerich, Mark E.
AU - Fennimore, Blair P.
AU - Ir, Diana
AU - Jubair, Widian K.
AU - Görg, Carsten
AU - Siebert, Janet
AU - Robertson, Charles E.
AU - Caplan, Liron
AU - Frank, Daniel N.
AU - Kuhn, Kristine A.
N1 - Funding Information:
This work was supported by grants from the National Center for Advancing Translational Science (UL1 TR001082 to NO), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32 AR007534 to NO and EHR), and the National Institute of Diabetes and Digestive and Kidney Diseases (K08DK107905 to KAK) at the National Institutes of Health. Additional support was provided by the Michelson charitable fund and the UC Denver Gastrointestinal and Liver Innate Immune Program (KAK, DNF, CER, DI). Dr Caplan is supported by VA MERIT IIR 14-083-03.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/7/20
Y1 - 2018/7/20
N2 - Background: Dysbiosis occurs in spondyloarthritis (SpA) and inflammatory bowel disease (IBD), which is subdivided into Crohn's disease (CD) and ulcerative colitis (UC). The immunologic consequences of alterations in microbiota, however, have not been defined. Intraepithelial lymphocytes (IELs) are T cells within the intestinal epithelium that are in close contact with bacteria and are likely to be modulated by changes in microbiota. We examined differences in human gut-associated bacteria and tested correlation with functional changes in IELs in patients with axial SpA (axSpA), CD, or UC, and in controls. Methods: We conducted a case-control study to evaluate IELs from pinch biopsies of grossly normal colonic tissue from subjects with biopsy-proven CD or UC, axSpA fulfilling Assessment of SpondyloArthritis International Society (ASAS) criteria and from controls during endoscopy. IELs were harvested and characterized by flow cytometry for cell surface markers. Secreted cytokines were measured by ELISA. Microbiome analysis was by 16S rRNA gene sequencing from rectal swabs. Statistical analyses were performed with the Kruskal-Wallis and Spearman's rank tests. Results: The total number of IELs was significantly decreased in subjects with axSpA compared to those with IBD and controls, likely due to a decrease in TCRβ+ IELs. We found strong, significant negative correlation between peripheral lymphocyte count and IEL number. IELs secreted significantly increased IL-1β in patients with UC, significantly increased IL-17A and IFN-γ in patients with CD, and significantly increased TNF-α in patients with CD and axSpA as compared to other cohorts. For each disease subtype, IELs and IEL-produced cytokines were positively and negatively correlated with the relative abundance of multiple bacterial taxa. Conclusions: Our data indicate differences in IEL function among subjects with axSpA, CD, and UC compared to healthy controls. We propose that the observed correlation between altered microbiota and IEL function in these populations are relevant to the pathogenesis of axSpA and IBD, and discuss possible mechanisms.
AB - Background: Dysbiosis occurs in spondyloarthritis (SpA) and inflammatory bowel disease (IBD), which is subdivided into Crohn's disease (CD) and ulcerative colitis (UC). The immunologic consequences of alterations in microbiota, however, have not been defined. Intraepithelial lymphocytes (IELs) are T cells within the intestinal epithelium that are in close contact with bacteria and are likely to be modulated by changes in microbiota. We examined differences in human gut-associated bacteria and tested correlation with functional changes in IELs in patients with axial SpA (axSpA), CD, or UC, and in controls. Methods: We conducted a case-control study to evaluate IELs from pinch biopsies of grossly normal colonic tissue from subjects with biopsy-proven CD or UC, axSpA fulfilling Assessment of SpondyloArthritis International Society (ASAS) criteria and from controls during endoscopy. IELs were harvested and characterized by flow cytometry for cell surface markers. Secreted cytokines were measured by ELISA. Microbiome analysis was by 16S rRNA gene sequencing from rectal swabs. Statistical analyses were performed with the Kruskal-Wallis and Spearman's rank tests. Results: The total number of IELs was significantly decreased in subjects with axSpA compared to those with IBD and controls, likely due to a decrease in TCRβ+ IELs. We found strong, significant negative correlation between peripheral lymphocyte count and IEL number. IELs secreted significantly increased IL-1β in patients with UC, significantly increased IL-17A and IFN-γ in patients with CD, and significantly increased TNF-α in patients with CD and axSpA as compared to other cohorts. For each disease subtype, IELs and IEL-produced cytokines were positively and negatively correlated with the relative abundance of multiple bacterial taxa. Conclusions: Our data indicate differences in IEL function among subjects with axSpA, CD, and UC compared to healthy controls. We propose that the observed correlation between altered microbiota and IEL function in these populations are relevant to the pathogenesis of axSpA and IBD, and discuss possible mechanisms.
KW - Crohn's disease
KW - Inflammatory bowel disease
KW - Intraepithelial lymphocytes
KW - Microbiome
KW - Spondyloarthritis
KW - Ulcerative colitis
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U2 - 10.1186/s13075-018-1639-3
DO - 10.1186/s13075-018-1639-3
M3 - Article
C2 - 30029674
AN - SCOPUS:85050297819
SN - 1478-6354
VL - 20
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 149
ER -