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STING Negatively Regulates Double-Stranded DNA-Activated JAK1-STAT1 Signaling via SHP-1/2 in B Cells
Dong, Guanjun,You, Ming,Ding, Liang,Fan, Hongye,Liu, Fei,Ren, Deshan,Hou, Yayi Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.5
Recognition of cytosolic DNA initiates a series of innate immune responses by inducing IFN-I production and subsequent triggering JAK1-STAT1 signaling which plays critical roles in the pathogenesis of infection, inflammation and autoimmune diseases through promoting B cell activation and antibody responses. The stimulator of interferon genes protein (STING) has been demonstrated to be a critical hub of type I IFN induction in cytosolic DNA-sensing pathways. However, it still remains unknown whether cytosolic DNA can directly activate the JAK1-STAT1 signaling or not. And the role of STING is also unclear in this response. In the present study, we found that dsDNA directly triggered the JAK1-STAT1 signaling by inducing phosphorylation of the Lyn kinase. Moreover, this response is not dependent on type I IFN receptors. Interestingly, STING could inhibit dsDNA-triggered activation of JAK1-STAT1 signaling by inducing SHP-1 and SHP-2 phosphorylation. In addition, compared with normal B cells, the expression of STING was significantly lower and the phosphorylation level of JAK1 was significantly higher in B cells from MRL/lpr lupus-prone mice, highlighting the close association between STING low-expression and JAK1-STAT1 signaling activation in B cells in autoimmune diseases. Our data provide a molecular insight into the novel role of STING in dsDNA-mediated inflammatory disorders.
STING Negatively Regulates Double-Stranded DNA-Activated JAK1-STAT1 Signaling via SHP-1/2 in B Cells
Yayi Hou,Guanjun Dong,Ming You,Liang Ding,Hongye Fan,Fei Liu,Deshan Ren 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.5
Recognition of cytosolic DNA initiates a series of innate immune responses by inducing IFN-I production and subsequent triggering JAK1-STAT1 signaling which plays critical roles in the pathogenesis of infection, inflammation and autoimmune diseases through promoting B cell activation and antibody responses. The stimulator of interferon genes protein (STING) has been demonstrated to be a critical hub of type I IFN induction in cytosolic DNA-sensing pathways. However, it still remains unknown whether cytosolic DNA can directly activate the JAK1-STAT1 signaling or not. And the role of STING is also unclear in this response. In the present study, we found that dsDNA directly triggered the JAK1-STAT1 signaling by inducing phosphorylation of the Lyn kinase. Moreover, this response is not dependent on type I IFN receptors. Interestingly, STING could inhibit dsDNA-triggered activation of JAK1-STAT1 signaling by inducing SHP-1 and SHP-2 phosphorylation. In addition, compared with normal B cells, the expression of STING was significantly lower and the phosphorylation level of JAK1 was significantly higher in B cells from MRL/lpr lupus-prone mice, highlighting the close association between STING low-expression and JAK1-STAT1 signaling activation in B cells in autoimmune diseases. Our data provide a molecular insight into the novel role of STING in dsDNA-mediated inflammatory disorders.
A Fiber Spool’s Vibration Sensitivity Optimization Based on Orthogonal Experimental Design
Jing Gao,Linbo Zhang,Dongdong Jiao,Guanjun Xu,Xue Deng,Qi Zang,Honglei Yang,Ruifang Dong,Tao Liu,Shougang Zhang 한국광학회 2024 Current Optics and Photonics Vol.8 No.1
A fiber spool with ultra-low vibration sensitivity has been demonstrated for the ultra-narrowlinewidth fiber-stabilized laser by the multi-object orthogonal experimental design method, which can achieve the optimization object and analysis of influence levels without extensive computation. According to a test of 4 levels and 4 factors, an L 16 (4 4 ) orthogonal table is established to design orthogonal experiments. The vibration sensitivities along the axial and radial directions and the normalized sums of the vibration sensitivities are determined as single objects and comprehensive objects, respectively. We adopt the range analysis of object values to obtain the influence levels of the four design parameters on the single objects and the comprehensive object. The optimal parameter combinations are determined by both methods of comprehensive balance and evaluation. Based on the corresponding fractional frequency stability of ultra-narrow-linewidth fiber-stabilized lasers, we obtain the final optimal parameter combination A3B1C2D1, which can achieve the fiber spool with vibration sensitivities of 10 −12 /g magnitude. This work is the first time to use an orthogonal experimental design method to optimize the vibration sensitivities of fiber spools, providing an approach to design the fiber spool with ultra-low vibration sensitivity.