Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis
Background: In Crohn’s disease and ulcerative colitis, the anti-α4β7 integrin antibody vedolizumab has demonstrated efficacy in phase III trials and has been successfully used under real-world conditions. Occasionally, it has also been used in other forms of inflammatory bowel disease (IBD) such as...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-06-01
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| Series: | Therapeutic Advances in Gastroenterology |
| Online Access: | https://doi.org/10.1177/17562848221098899 |
| _version_ | 1811332022085353472 |
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| author | Laura Besendorf Tanja M. Müller Carol-Immanuel Geppert Ines Schneider Laura Mühl Imke Atreya Francesco Vitali Raja Atreya Markus F. Neurath Sebastian Zundler |
| author_facet | Laura Besendorf Tanja M. Müller Carol-Immanuel Geppert Ines Schneider Laura Mühl Imke Atreya Francesco Vitali Raja Atreya Markus F. Neurath Sebastian Zundler |
| author_sort | Laura Besendorf |
| collection | DOAJ |
| description | Background: In Crohn’s disease and ulcerative colitis, the anti-α4β7 integrin antibody vedolizumab has demonstrated efficacy in phase III trials and has been successfully used under real-world conditions. Occasionally, it has also been used in other forms of inflammatory bowel disease (IBD) such as microscopic colitis (MC). However, the mechanisms of vedolizumab in MC have not been studied to date. Therefore, we aimed to investigate the expression and functional role of gut-homing integrins and in particular α4β7 integrin in a cohort study in MC. Methods: We studied the expression of gut homing integrins on T cells from patients with MC and healthy controls by flow cytometry. To investigate the function of α4β7 integrin in MC and the potential of vedolizumab to block it, we used dynamic adhesion assays and transmigrations assays. Moreover, we describe two clinical cases of MC patients treated with vedolizumab. Results: A specific profile of gut homing markers can be found on T cells from patients with MC. α4β7 integrin functionally leads to firm adhesion to MAdCAM-1 and supports transmigration. Vedolizumab is able to block both processes. In two cases of MC, we observed reduced clinical symptoms and histologic improvement upon therapy with vedolizumab. Conclusion: Our data suggest that α4β7 mediates gut homing of T cells also in MC and that, on single cell level, vedolizumab blocks the function of α4β7 in MC. Thus, we provide mechanistic evidence supporting vedolizumab as promising therapeutic option for MC. |
| first_indexed | 2024-04-13T16:29:37Z |
| format | Article |
| id | doaj.art-5b27385d3bef4b26abc5f732eaad5abb |
| institution | Directory Open Access Journal |
| issn | 1756-2848 |
| language | English |
| last_indexed | 2024-04-13T16:29:37Z |
| publishDate | 2022-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Gastroenterology |
| spelling | doaj.art-5b27385d3bef4b26abc5f732eaad5abb2022-12-22T02:39:37ZengSAGE PublishingTherapeutic Advances in Gastroenterology1756-28482022-06-011510.1177/17562848221098899Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitisLaura BesendorfTanja M. MüllerCarol-Immanuel GeppertInes SchneiderLaura MühlImke AtreyaFrancesco VitaliRaja AtreyaMarkus F. NeurathSebastian ZundlerBackground: In Crohn’s disease and ulcerative colitis, the anti-α4β7 integrin antibody vedolizumab has demonstrated efficacy in phase III trials and has been successfully used under real-world conditions. Occasionally, it has also been used in other forms of inflammatory bowel disease (IBD) such as microscopic colitis (MC). However, the mechanisms of vedolizumab in MC have not been studied to date. Therefore, we aimed to investigate the expression and functional role of gut-homing integrins and in particular α4β7 integrin in a cohort study in MC. Methods: We studied the expression of gut homing integrins on T cells from patients with MC and healthy controls by flow cytometry. To investigate the function of α4β7 integrin in MC and the potential of vedolizumab to block it, we used dynamic adhesion assays and transmigrations assays. Moreover, we describe two clinical cases of MC patients treated with vedolizumab. Results: A specific profile of gut homing markers can be found on T cells from patients with MC. α4β7 integrin functionally leads to firm adhesion to MAdCAM-1 and supports transmigration. Vedolizumab is able to block both processes. In two cases of MC, we observed reduced clinical symptoms and histologic improvement upon therapy with vedolizumab. Conclusion: Our data suggest that α4β7 mediates gut homing of T cells also in MC and that, on single cell level, vedolizumab blocks the function of α4β7 in MC. Thus, we provide mechanistic evidence supporting vedolizumab as promising therapeutic option for MC.https://doi.org/10.1177/17562848221098899 |
| spellingShingle | Laura Besendorf Tanja M. Müller Carol-Immanuel Geppert Ines Schneider Laura Mühl Imke Atreya Francesco Vitali Raja Atreya Markus F. Neurath Sebastian Zundler Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis Therapeutic Advances in Gastroenterology |
| title | Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis |
| title_full | Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis |
| title_fullStr | Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis |
| title_full_unstemmed | Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis |
| title_short | Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis |
| title_sort | vedolizumab blocks α4β7 integrin mediated t cell adhesion to madcam 1 in microscopic colitis |
| url | https://doi.org/10.1177/17562848221098899 |
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