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 gamma (IFN-gamma)-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.
[1]Univ Chinese Acad Sci, State Key Lab Cell Biol, Chinese Acad Sci,Key Lab Syst Biol,Innovat Ctr Ce, Shanghai Inst Biochem & Cell Biol,CAS Ctr Excelle, Shanghai 200031, Peoples R China.
[2]Shanghai Univ, Coll Life Sci, Shanghai 200444, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Spine Dis, Shanghai, Peoples R China.
[4]NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[5]Tongji Univ, Shanghai Peoples Hosp 10, Canc Ctr, Sch Med, Shanghai 200072, Peoples R China.
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