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Perfluorooctanesulfonic acid modulates barrier function and systemic T-cell homeostasis during intestinal inflammation

Diaz, Oscar E. ; Sorini, Chiara ; Morales, Rodrigo A. ; Luo, Xinxin ; Frede, Annika ; Krais, Annette M. LU orcid ; Chávez, Myra N. ; Wincent, Emma ; Das, Srustidhar and Villablanca, Eduardo J. (2021) In DMM Disease Models and Mechanisms 14(12). p.1-11
Abstract

The intestinal epithelium is continuously exposed to deleterious environmental factors that might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are 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, which have been positively associated with ulcerative colitis incidence. Exposure to perfluorooctanesulfonic acid (PFOS) during 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced inflammation enhanced the expression of proinflammatory cytokines as... (More)

The intestinal epithelium is continuously exposed to deleterious environmental factors that might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are 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, which have been positively associated with ulcerative colitis incidence. Exposure to perfluorooctanesulfonic acid (PFOS) during 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced inflammation enhanced the expression of proinflammatory cytokines as well as neutrophil recruitment to the intestine of zebrafish larvae, which was validated in the TNBS-induced colitis mouse model. Moreover, PFOS exposure in mice undergoing colitis resulted in neutrophil-dependent increased intestinal permeability and enhanced PFOS translocation into the circulation. 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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Colitis, Experimental models, Inflammation, Pollutants, T cell
in
DMM Disease Models and Mechanisms
volume
14
issue
12
article number
dmm049104
pages
1 - 11
publisher
The Company of Biologists Ltd
external identifiers
  • pmid:34792120
  • scopus:85121980839
  • pmid:34792120
ISSN
1754-8411
DOI
10.1242/dmm.049104
language
English
LU publication?
yes
id
7cb94583-1e62-4de5-9d58-8d2e4c151197
date added to LUP
2022-01-24 20:01:15
date last changed
2024-06-17 03:01:41
@article{7cb94583-1e62-4de5-9d58-8d2e4c151197,
  abstract     = {{<p>The intestinal epithelium is continuously exposed to deleterious environmental factors that might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are 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, which have been positively associated with ulcerative colitis incidence. Exposure to perfluorooctanesulfonic acid (PFOS) during 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced inflammation enhanced the expression of proinflammatory cytokines as well as neutrophil recruitment to the intestine of zebrafish larvae, which was validated in the TNBS-induced colitis mouse model. Moreover, PFOS exposure in mice undergoing colitis resulted in neutrophil-dependent increased intestinal permeability and enhanced PFOS translocation into the circulation. This was associated with a neutrophil-dependent expansion of systemic CD4<sup>+</sup> 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.</p>}},
  author       = {{Diaz, Oscar E. and Sorini, Chiara and Morales, Rodrigo A. and Luo, Xinxin and Frede, Annika and Krais, Annette M. and Chávez, Myra N. and Wincent, Emma and Das, Srustidhar and Villablanca, Eduardo J.}},
  issn         = {{1754-8411}},
  keywords     = {{Colitis; Experimental models; Inflammation; Pollutants; T cell}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{1--11}},
  publisher    = {{The Company of Biologists Ltd}},
  series       = {{DMM Disease Models and Mechanisms}},
  title        = {{Perfluorooctanesulfonic acid modulates barrier function and systemic T-cell homeostasis during intestinal inflammation}},
  url          = {{http://dx.doi.org/10.1242/dmm.049104}},
  doi          = {{10.1242/dmm.049104}},
  volume       = {{14}},
  year         = {{2021}},
}