Diaz, Oscar E; Sorini, Chiara; Morales, Rodrigo A; Luo, Xinxin; Frede, Annika; Krais, Annette M; Chavez, Myra N; Wincent, Emma; Das, Srustidhar; Villablanca, Eduardo J (2021). Perfluorooctanesulfonic acid modulates barrier function and systemic T cell homeostasis during intestinal inflammation. Disease models & mechanisms, 14(12), pp. 1-11. Company of Biologists Ltd. 10.1242/dmm.049104
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The intestinal epithelium is continuously exposed to deleterious environmental factors which might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are yet poorly understood. Here, to overcome the lack of in vivo models suitable for screening of environmental factors we used zebrafish reporters of intestinal inflammation. Using zebrafish, we interrogated the immunomodulatory effects of polyfluoroalkyl substances (PFAS), which have been positively associated with ulcerative colitis incidence. Exposure with perfluorooctanesulfonic acid (PFOS) during TNBS-induced inflammation enhances the expression of proinflammatory cytokines as well as neutrophil recruitment to the intestine of zebrafish larvae, which was validated in TNBS-induced colitis mice models. Moreover, PFOS exposure in mice undergoing colitis resulted in neutrophil-dependent increased intestinal permeability and enhanced PFOS translocation into circulation. Finally, this was associated with a neutrophil dependent expansion of systemic CD4+ T cells. Thus, our results indicate that PFOS worsens inflammation-induced intestinal damage with disruption of T cell homeostasis beyond the gut and provides a novel in vivo toolbox to screen for pollutants affecting intestinal homeostasis.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy |
UniBE Contributor: |
Chavez Rosas, Myra Noemi |
ISSN: |
1754-8403 |
Publisher: |
Company of Biologists Ltd. |
Language: |
English |
Submitter: |
Nadia Isabel Mercader Huber |
Date Deposited: |
04 Jan 2022 12:30 |
Last Modified: |
05 Dec 2022 15:56 |
Publisher DOI: |
10.1242/dmm.049104 |
PubMed ID: |
34792120 |
Uncontrolled Keywords: |
Colitis Experimental models Inflammation Pollutants T cell |
BORIS DOI: |
10.48350/162210 |
URI: |
https://boris.unibe.ch/id/eprint/162210 |
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