PUBLICATION
Perfluorooctanesulfonic acid modulates barrier function and systemic T cell homeostasis during intestinal inflammation
- Authors
- Diaz, O.E., Sorini, C., Morales, R.A., Luo, X., Frede, A., Krais, A.M., Chávez, M.N., Wincent, E., Das, S., Villablanca, E.J.
- ID
- ZDB-PUB-211119-5
- Date
- 2021
- Source
- Disease models & mechanisms 14(12): (Journal)
- Registered Authors
- Das, Srustidhar, Diaz, Oscar E., Frede, Annika, Luo, Xinxin, Morales Castro, Rodrigo A., Sorini, Chiara, Villablanca, Eduardo J.
- Keywords
- Colitis, Experimental models, Inflammation, Pollutants, T cell
- MeSH Terms
-
- Alkanesulfonic Acids
- Animals
- Colitis*/chemically induced
- Colitis*/metabolism
- Cytokines/metabolism
- Disease Models, Animal
- Fluorocarbons
- Homeostasis
- Inflammation/metabolism
- Intestinal Mucosa/metabolism
- Mice
- Trinitrobenzenesulfonic Acid/adverse effects
- Trinitrobenzenesulfonic Acid/metabolism
- Zebrafish*/metabolism
- PubMed
- 34792120 Full text @ Dis. Model. Mech.
Citation
Diaz, O.E., Sorini, C., Morales, R.A., Luo, X., Frede, A., Krais, A.M., Chávez, M.N., Wincent, E., Das, S., Villablanca, E.J. (2021) Perfluorooctanesulfonic acid modulates barrier function and systemic T cell homeostasis during intestinal inflammation. Disease models & mechanisms. 14(12):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping