Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota
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 (IEL...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-018-1639-3 |
| _version_ | 1818857853069295616 |
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| author | Emilie H. Regner Neha Ohri Andrew Stahly Mark E. Gerich Blair P. Fennimore Diana Ir Widian K. Jubair Carsten Görg Janet Siebert Charles E. Robertson Liron Caplan Daniel N. Frank Kristine A. Kuhn |
| author_facet | Emilie H. Regner Neha Ohri Andrew Stahly Mark E. Gerich Blair P. Fennimore Diana Ir Widian K. Jubair Carsten Görg Janet Siebert Charles E. Robertson Liron Caplan Daniel N. Frank Kristine A. Kuhn |
| author_sort | Emilie H. Regner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T08:46:59Z |
| format | Article |
| id | doaj.art-2f3c934788b644c195e2907880a4dd37 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-19T08:46:59Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-2f3c934788b644c195e2907880a4dd372022-12-21T20:28:47ZengBMCArthritis Research & Therapy1478-63622018-07-0120111310.1186/s13075-018-1639-3Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiotaEmilie H. Regner0Neha Ohri1Andrew Stahly2Mark E. Gerich3Blair P. Fennimore4Diana Ir5Widian K. Jubair6Carsten Görg7Janet Siebert8Charles E. Robertson9Liron Caplan10Daniel N. Frank11Kristine A. Kuhn12Division of Gastroenterology, Department of Medicine, University of Colorado School of MedicineDivision of Rheumatology, Department of Medicine, University of Colorado School of MedicineDivision of Rheumatology, Department of Medicine, University of Colorado School of MedicineDivision of Gastroenterology, Department of Medicine, University of Colorado School of MedicineDivision of Gastroenterology, Department of Medicine, University of Colorado School of MedicineDivision of Infectious Disease, Department of Medicine, University of Colorado School of MedicineDivision of Rheumatology, Department of Medicine, University of Colorado School of MedicineComputational Bioscience Program, University of Colorado School of MedicineComputational Bioscience Program, University of Colorado School of MedicineDivision of Infectious Disease, Department of Medicine, University of Colorado School of MedicineDivision of Rheumatology, Department of Medicine, University of Colorado School of MedicineDivision of Infectious Disease, Department of Medicine, University of Colorado School of MedicineDivision of Rheumatology, Department of Medicine, University of Colorado School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s13075-018-1639-3Inflammatory bowel diseaseUlcerative colitisCrohn’s diseaseSpondyloarthritisIntraepithelial lymphocytesMicrobiome |
| spellingShingle | Emilie H. Regner Neha Ohri Andrew Stahly Mark E. Gerich Blair P. Fennimore Diana Ir Widian K. Jubair Carsten Görg Janet Siebert Charles E. Robertson Liron Caplan Daniel N. Frank Kristine A. Kuhn Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota Arthritis Research & Therapy Inflammatory bowel disease Ulcerative colitis Crohn’s disease Spondyloarthritis Intraepithelial lymphocytes Microbiome |
| title | Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota |
| title_full | Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota |
| title_fullStr | Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota |
| title_full_unstemmed | Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota |
| title_short | Functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota |
| title_sort | functional intraepithelial lymphocyte changes in inflammatory bowel disease and spondyloarthritis have disease specific correlations with intestinal microbiota |
| topic | Inflammatory bowel disease Ulcerative colitis Crohn’s disease Spondyloarthritis Intraepithelial lymphocytes Microbiome |
| url | http://link.springer.com/article/10.1186/s13075-018-1639-3 |
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