Epithelial HIF2 alpha expression induces intestinal barrier dysfunction and exacerbation of arthritis

Wen J, Lyu P, Stolzer I, Xu J, Gießl A, Lin Z, Andreev D, Kachler K, Song R, Meng X, Cao S, Guggino G, Ciccia F, Günther C, Schett G, Bozec A (2022)


Publication Language: English

Publication Type: Journal article, other

Publication year: 2022

Journal

URI: https://ard.bmj.com/content/81/8/1119

DOI: 10.1136/annrheumdis-2021-222035

Abstract

To investigate how the mucosal barrier in the intestine influences the development of arthritis, considering that metabolic changes in the intestinal epithelium influence its barrier function. Intestinal HIF2α expression peaked at onset of experimental arthritis and RA. Conditionally, deletion of HIF2α in gut epithelial cells inhibited arthritis and was associated with improved intestinal barrier function and less intestinal and lymphatic Th1 and Th17 activation. Mechanistically, HIF2α induced the transcription of the pore-forming claudin (CLDN)-15, which inhibits intestinal barrier integrity. Furthermore, treatment with HIF2α inhibitor decreased claudin-15 expression in epithelial cells and inhibited arthritis and littermate control mice. The gut intestinal HIF2α target genes were delineated by chromatin immunoprecipitation and luciferase experiments. Furthermore, pharmacological HIF2α inhibitor PT2977 was used for inhibition of arthritis. These findings show that the HIF2α-CLDN15 axis is critical for the breakdown of intestinal barrier function at onset of arthritis, highlighting the functional link between intestinal homeostasis and arthritis.

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How to cite

APA:

Wen, J., Lyu, P., Stolzer, I., Xu, J., Gießl, A., Lin, Z.,... Bozec, A. (2022). Epithelial HIF2 alpha expression induces intestinal barrier dysfunction and exacerbation of arthritis. Annals of the Rheumatic Diseases. https://dx.doi.org/10.1136/annrheumdis-2021-222035

MLA:

Wen, Jinming, et al. "Epithelial HIF2 alpha expression induces intestinal barrier dysfunction and exacerbation of arthritis." Annals of the Rheumatic Diseases (2022).

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