Naive T Cells in the Gut of Newly Diagnosed, Untreated Adult Patients with Inflammatory Bowel Disease

Horje, Carmen S. Horjus Talabur; Middendorp, Sabine; Koolwijk, Elly van; Roovers, L.; Groenen, Marcel; Wahab, Peter J.; Lochem, Ellen G. van

doi:10.1097/mib.0000000000000203

Cited by 16 publications

(14 citation statements)

References 40 publications

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“…Our findings suggest differences between IBD patients, both UC and CD, regarding TLO formation and recruitment of different lymphocyte subsets to the inflamed gut mucosa. These results expand further on our previous paper in newly diagnosed IBD patients with increased numbers of T N and T CM cells in the inflamed gut of a subgroup of patients [7]. Taken together, our results point out that increased homing of T N and T CM lymphocytes to non-lymphoid gut tissue in a subgroup of IBD patients might be facilitated by de-novo formation of extrafollicular HEVs and TLOs.…”

Section: Hevs and T Cell Subsets In Early Ibdsupporting

confidence: 91%

“…We and others have demonstrated the presence of T N and T CM lymphocytes in non-lymphoid gut tissue [7][8][9][10][11]. In our previous work, we identified three subgroups of newly diagnosed IBD patients with either increased percentage of mucosal T N , T CM or T EM [7]. It is still unclear how homing of these T N and T CM lymphocytes to nonlymphoid tissue is established.…”

Section: Introductionmentioning

confidence: 91%

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High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients

Horje

Smids

Meijer

et al. 2017

Clinical and Experimental Immunology

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Naive and central memory T lymphocytes (T and T ) can infiltrate the inflamed gut mucosa in inflammatory bowel disease (IBD) patients. Homing of these subsets to the gut might be explained by ectopic formation of tertiary lymphoid organs (TLOs), containing high endothelial venules (HEVs). We aimed to evaluate the presence of HEVs and TLOs in inflamed intestinal mucosa of newly diagnosed, untreated IBD patients in relation to the presence of T and T lymphocytes. IBD patients (n = 39) and healthy controls (n = 8) were included prospectively. Biopsy samples of inflamed and normal intestine, respectively, were analysed by immunohistochemistry for lymphocytes (CD3/CD20), blood vessels (CD31) and peripheral lymph node addressin (PNAd) expression (MECA-79). T and T lymphocyte subsets were identified by flow cytometric immunophenotyping. A higher number of HEVs was found in the inflamed colon of patients with ulcerative colitis [median 3·05 HEV/mm ; interquartile range (IQR) = 0-6·39] and ileum of Crohn's disease patients (1·40; 0-4·34) compared to healthy controls (both 0; P = 0·033). A high density of colonic HEVs (HEV ) was associated with increased infiltration of T and T in the inflamed gut (median 87%; IQR = 82-93% of T cell population), compared to HEV patients (58%; 38-81%; P = 0·003). The number of colonic follicles was higher in HEV patients (median 0·54/mm ; IQR 0·28-0·84) compared to HEV patients (0·25/mm ; 0·08-0·45; P = 0·031) and controls (0·31/mm ; 0·23-0·45; P = 0·043). Increased homing of T and T lymphocytes to inflamed gut tissue in IBD patients might be facilitated by ectopic formation of extrafollicular HEVs and TLOs in a subgroup of patients.

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Section: Hevs and T Cell Subsets In Early Ibdsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 91%

High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients

Horje

Smids

Meijer

et al. 2017

Clinical and Experimental Immunology

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“…A previous study using flow cytometry and a mixture of ileal and colonic biopsies also found a reduced number of αE + cells in IBD biopsies. 37 The effect on αE + cell numbers and inflammatory cytokine production by these cells should be further investigated in CD, as cell numbers may not wholly reflect inflammatory potential. Correlation between αE + cells was observed between matched ileal and colonic biopsies.…”

Section: Discussionmentioning

confidence: 99%

AlphaE Integrin Expression Is Increased in the Ileum Relative to the Colon and Unaffected by Inflammation

Ichikawa¹,

Lamb

Eastham-Anderson³

et al. 2018

Journal of Crohn's and Colitis

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BackgroundRecent findings suggest that αE expression is enriched on effector T cells and that intestinal αE+ T cells have increased expression of inflammatory cytokines. αE integrin expression is a potential predictive biomarker for response to etrolizumab, a monoclonal antibody against β7 integrin that targets both α4β7 and αEβ7. We evaluated the prevalence and localization of αE+ cells as well as total αE gene expression in healthy and inflammatory bowel disease patients.MethodsαE+ cells were identified in ileal and colonic biopsies by immunohistochemistry and counted using an automated algorithm. Gene expression was assessed by quantitative reverse-transcriptase polymerase chain reaction.ResultsIn both healthy and inflammatory bowel disease patients, significantly more αE+ cells were present in the epithelium and lamina propria of ileal compared with colonic biopsies. αE gene expression levels were also significantly higher in ileal compared with colonic biopsies. Paired biopsies from the same patient showed moderate correlation of αE expression between the ileum and colon. Inflammation did not affect αE expression, and neither endoscopy nor histology scores correlated with αE gene expression. αE expression was not different between patients based on concomitant medication use except 5-aminosalicylic acid.ConclusionαE+ cells, which have been shown to have inflammatory potential, are increased in the ileum in comparison with the colon in both Crohn’s disease and ulcerative colitis, as well as in healthy subjects. In inflammatory bowel disease patients, αE levels are stable, regardless of inflammatory status or most concomitant medications, which could support its use as a biomarker for etrolizumab.

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“…Naïve T cells can share the same TCRβ nucleotide sequence but have different TCRα sequences [20]. Therefore, in order to omit TCRβ nucleotide clonotypes that might originate from naïve T cells [22][23][24][25] and to focus on the more expanded clonotypes (here designated as 'memory TCRβ repertoire') we used a clonotype frequency of 0.01% as a threshold for further analysis.…”

Section: Gut and Liver Memory T Cells Of Common Clonal Origin Are Detmentioning

confidence: 99%

Gut and liver T-cells of common clonal origin in primary sclerosing cholangitis-inflammatory bowel disease

Henriksen

Jørgensen

Kaveh

et al. 2017

Journal of Hepatology

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Primary sclerosing cholangitis (PSC) is a devastating liver disease strongly associated with inflammatory bowel disease (IBD). The cause of PSC is unknown, but it has been suggested that the immune reactions in the gut and the liver are connected. Our data demonstrate for the first time that a proportion of the T-cells in the gut and the liver react to similar triggers, and that this proportion is particularly high in patients with PSC and IBD.

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Naive T Cells in the Gut of Newly Diagnosed, Untreated Adult Patients with Inflammatory Bowel Disease

Abstract: Newly diagnosed patients with inflammatory bowel disease display different T-cell maturation profiles in the gut mucosa, corresponding to distinct cytokine responses. Follow-up studies are needed to determine whether the profiles associate with clinical course and response to therapy.

Cited by 16 publications

References 40 publications

High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients

High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients

AlphaE Integrin Expression Is Increased in the Ileum Relative to the Colon and Unaffected by Inflammation

Gut and liver T-cells of common clonal origin in primary sclerosing cholangitis-inflammatory bowel disease

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