Faculty Collaboration Database

Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota. Arthritis Res Ther 2018 Jul 20;20(1):149

Date

07/22/2018

Pubmed ID

30029674

Pubmed Central ID

PMC6053728

DOI

10.1186/s13075-018-1639-3

Scopus ID

2-s2.0-85050297819 (requires institutional sign-in at Scopus site)   47 Citations

Abstract

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.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02389075 . Registered on 17 March 2015.

Author List

Regner EH, Ohri N, Stahly A, Gerich ME, Fennimore BP, Ir D, Jubair WK, Görg C, Siebert J, Robertson CE, Caplan L, Frank DN, Kuhn KA

Author

Emilie Regner MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Case-Control Studies
Female
Gastrointestinal Microbiome
Humans
Inflammatory Bowel Diseases
Intraepithelial Lymphocytes
Male
Middle Aged
Spondylarthritis