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The transcription factor NFIL3 controls regulatory T-cell function and stability
김형수,Hyogon Sohn,Sung Woong Jang,이갑열 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
Regulatory T (Treg) cells are a CD4 T-cell subset with an important role in immune tolerance; however, the mechanisms underlying Treg cell differentiation and function are incompletely understood. Here, we show that NFIL3/ E4BP4, a transcription factor, plays a key role in Treg cell differentiation and function. Microarray analysis showed that Treg cells had lower Nfil3 expression than all other CD4 T-cell subsets. Overexpression of Nfil3 in Treg cells led to diminished expression of Foxp3 and other signature Treg genes, including Il2ra, Icos, Tnfrsf18, and Ctla4. Furthermore, Nfil3-overexpressing Treg cells exhibited impaired immunosuppressive activity in vitro and in vivo. We discovered that NFIL3 directly binds to and negatively regulates the expression of Foxp3. In addition, bisulfite sequencing revealed that NFIL3 induces methylation at Foxp3 locus regulatory CpG sites, which contributes to the control of Treg cell stability. Together, these data indicate that NFIL3 impairs Treg cell function through the downregulation of Foxp3 expression.
PTEN drives Th17 cell differentiation by preventing IL-2 production
Kim, Hyeong Su,Jang, Sung Woong,Lee, Wonyong,Kim, Kiwan,Sohn, Hyogon,Hwang, Soo Seok,Lee, Gap Ryol The Rockefeller University Press 2017 The Journal of experimental medicine Vol.214 No.11
<▼1><P>Th17 cells mediate inflammation and autoimmunity. Although it was known that cytokine IL-2 inhibits Th17 cell differentiation, how it does so was elusive. Using IL-17–specific PTEN-deficient mice, Kim et al. show that phosphatase PTEN inhibits IL-2 production and thus promotes Th17 cell differentiation.</P></▼1><▼2><P>T helper 17 (Th17) cells are a CD4<SUP>+</SUP> T cell subset that produces IL-17A to mediate inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However, the mechanism by which IL-2 is suppressed during Th17 cell differentiation remains unclear. Here, we show that phosphatase and tensin homologue (PTEN) is a key factor that regulates Th17 cell differentiation by suppressing IL-2 production. Th17-specific <I>Pten</I> deletion (<I>Pten<SUP>fl/fl</SUP>Il17a<SUP>cre</SUP></I>) impairs Th17 cell differentiation in vitro and ameliorated symptoms of experimental autoimmune encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease. Mechanistically, <I>Pten</I> deficiency up-regulates IL-2 and phosphorylation of STAT5, but reduces STAT3 phosphorylation, thereby inhibiting Th17 cell differentiation. PTEN inhibitors block Th17 cell differentiation in vitro and in the EAE model. Thus, PTEN plays a key role in Th17 cell differentiation by blocking IL-2 expression.</P></▼2>