Cell Reports
Volume 27, Issue 4, 23 April 2019, Pages 1176-1189.e5
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Article
YAP Aggravates Inflammatory Bowel Disease by Regulating M1/M2 Macrophage Polarization and Gut Microbial Homeostasis

https://doi.org/10.1016/j.celrep.2019.03.028Get rights and content
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Highlights

  • Myeloid-specific knockout of YAP relieves inflammatory bowel disease (IBD)

  • YAP regulates the balance between M1 and M2 polarization

  • YAP expression is differentially regulated by LPS/IFN-γ and IL-4/13 treatment

  • YAP in macrophages affects the abundance of gut microbiota in IBD mice

Summary

Inflammation, epithelial cell regeneration, macrophage polarization, and gut microbial homeostasis are critical for the pathological processes associated with inflammatory bowel disease (IBD). YAP (Yes-associated protein) is a key component of the Hippo pathway and was recently suggested to promote epithelial cell regeneration for IBD recovery. However, it is unclear how YAP regulates macrophage polarization, inflammation, and gut microbial homeostasis. Although YAP has been shown to promote epithelial regeneration and alleviate IBD, here we show that YAP in macrophages aggravates IBD, accompanied by the production of antimicrobial peptides and changes in gut microbiota. YAP impairs interleukin-4 (IL-4)/IL-13-induced M2 macrophage polarization while promoting lipopolysaccharide (LPS)/interferon γ (IFN-γ)-triggered M1 macrophage activation for IL-6 production. In addition, YAP expression is differently regulated during the induction of M2 versus M1 macrophages. This study suggests that fully understanding the multiple functions of YAP in different cell types is crucial for IBD therapy.

Keywords

YAP
macrophage polarization
inflammation
interleukin-6
IL-6
inflammatory bowel disease
IBD
microbiota
Hippo pathway

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