TSLP up‐regulates inflammatory responses through induction of autophagy in T cells. Issue 2 (8th January 2022)

• Record Type: Journal Article
• Authors: Han, Na‐Ra; Moon, Phil‐Dong; Nam, Sun‐Young; Ko, Seong‐Gyu; Park, Hi‐Joon; Kim, Hyung‐Min; Jeong, Hyun‐Ja
• Is Part Of: FASEB journal. Volume 36:Issue 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-08
• Subjects: autophagy -- EL4 cells -- inflammatory responses -- thymic stromal lymphopoietin; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202101447R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Thymic stromal lymphopoietin (TSLP), a type I cytokine belonging to the IL‐2 cytokine family, promotes Th2‐mediated inflammatory responses. The aim of this study is to investigate whether TSLP increases inflammatory responses via induction of autophagy using a murine T cell lymphoma cell line, EL4 cells, and lipopolysaccharide (LPS)‐injected mice. TSLP increased expression levels of autophagy‐related factors, such as Beclin‐1, LC3‐II, p62, Atg5, and lysosome associated membrane protein 1/2, whereas these factors increased by TSLP disappeared by neutralization of TSLP in EL4 cells. TSLP activated JAK1/JAK2/STAT5/JNK/PI3K, while the blockade of JAK1/JAK2/STAT5/JNK/PI3K signaling pathways reduced the expression levels of Beclin‐1, LC3‐II, and p62 in TSLP‐stimulated EL4 cells. In addition, TSLP simultaneously increased levels of inflammatory cytokines via induction of autophagy by activation of JAK1/JAK2/STAT5/JNK/PI3K signaling pathways. In an LPS‐induced acute liver injury (ALI) mouse model, exogenous TSLP increased expression levels of Beclin‐1 and LC3‐II, whereas functional deficiency of TSLP by TSLP siRNA resulted in lower expression of Beclin‐1, LC3‐II, and inflammatory cytokines, impairing their ability to form autophagosomes in ALI mice. Thus, our findings show a new role of TSLP between autophagy and inflammatory responses. In conclusion, regulating TSLP‐induced autophagy may be a potential therapeutic strategy for inflammatory responses.