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| 1 | S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission显示文摘Graft-versus-host disease (GVHD) significantly contributes to patient morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HSCT). Sphingosine-1-phosphate (S1P) signaling is involved in the biogenetic processes of different immune cells. In the current study, we demonstrated that recipient sphingosine kinase 1 (Sphk1), but not Sphk2, was required for optimal S1PR1-dependent donor T-cell allogeneic responses by secreting S1P. Using genetic and pharmacologic approaches, we demonstrated that inhibition of Sphk1 or S1PR1 substantially attenuated acute GVHD (aGVHD) while retaining the graft-versus-leukemia (GVL) effect. At the cellular level, the Sphk1/S1P/S1PR1 pathway differentially modulated the alloreactivity of CD4+ and CD8+ T cells;it facilitated T-cell differentiation into Th1/Th17 cells but not Tregs and promoted CD4+ T-cell infiltration into GVHD target organs but was dispensable for the CTL activity of allogeneic CD8+ T cells. At the molecular level, the Sphk1/S1P/S1PR1 pathway augmented mitochondrial fission and increased mitochondrial mass in allogeneic CD4+ but not CD8+ T cells by activating the AMPK/AKT/mTOR/Drp1 pathway, providing a mechanistic basis for GVL maintenance when S1P signaling was inhibited. For translational purposes, we detected the regulatory efficacy of pharmacologic inhibitors of Sphk1 and S1PR1 in GVHD induced by human T cells in a xenograft model. Our study provides novel mechanistic insight into how the Sphk1/S1P/S1PR1 pathway modulates T-cell alloreactivity and validates Sphk1 or S1PR1 as a therapeutic target for the prevention of GVHD and leukemia relapse. This novel strategy may be readily translated into the clinic to benefit patients with hematologic malignancies and disorders. | Linlu Tian Yongxia Wu Hee-Jin Choi Xiaohui Sui Xinlei Li M.Hanief Sofi Mohamed Faisal Kassir Xiao Chen Shikhar Mehrotra Besim Ogretmen Xue-zhong Yu | 2022 | Cellular & Molecular Immunology2022，19，11： | 2 |
| 2 | STING negatively regulates allogeneic T-cell responses by constraining antigen-presenting cell function显示文摘Stimulator of interferon genes(STING)-mediated innate immune activation plays a key role in tumor-and self-DNA-elicited antitumor immunity and autoimmunity.However,STING can also suppress tumor immunity and autoimmunity.STING signaling In host nonhematopoietic cells was reported to either protect against or promote graft-versus-host disease(GVHD),a major complication of allogeneic hematopoietic cell transplantation(allo-HCT).Host hematopoietic antigen-presenting cells(APCs)play key roles in donor T-cell priming during GVHD initiation.However,how STING regulates host hematopoietic APCs after allo-HCT remains unknown.We utilized murine models of allo-HCT to assess the role of STING in hematopoietic APCs.STING-deficient recipients developed more severe GVHD after major histocompatibility complex-mismatched allo-HCT.Using bone marrow chimeras,we found that STING deficiency in host hematopoietic cells was primarily responsible for exacerbating the disease.Furthermore,STING on host CD11c+cells played a dominant role in suppressing allogeneic T-cell responses.Mechanistically,STING deficiency resulted in increased survival,activation,and function of APCs,including macrophages and dendritic cells.Consistently,constitutive activation of STING attenuated the survival,activation,and function of APCs isolated from STING V154M knock-in mice.STING-deficient APCs augmented donor T-cell expansion,chemokine receptor expression,and migration into intestinal tissues,resulting in accelerated/exacerbated GVHD.Using pharmacologic approaches,we demonstrated that systemic administration of a STING agonist(bis-(3'-5')-cyclic dimeric guanosine monophosphate)to recipient mice before transplantation significantly reduced GVHD mortality.In conclusion,we revealed a novel role of STING in APC activity that dictates T-cell allogeneic responses and validated STING as a potential therapeutic target for controlling GVHD after allo-HCT. | Hee-Jin ChoiTaylor Ticer Yongxia Wu Chih-Hang Anthony Tang Corey Mealer David Bastian M.Hanief Sofi Linlu Tian Steven Schutt Hee-Jin Choi Taylor Ticer Mengmeng Zhang Xiaohui Sui Lei Huang Andrew L.Mellor Chih-Chi Andrew Hu Xue-Zhong Yu | 2021 | Cellular & Molecular Immunology2021，18，3： | 0 |
| 3 | Improving the band alignment at PtSe_(2)grain boundaries with selective adsorption of TCNQ显示文摘Grain boundaries in two-dimensional(2D)semiconductors generally induce distorted band alignment and interfacial charge,which impair their electronic properties for device applications.Here,we report the improvement of band alignment at the grain boundaries of PtSe_(2),a 2D semiconductor,with selective adsorption of a presentative organic acceptor,tetracyanoquinodimethane(TCNQ).TCNQ molecules show selective adsorption at the PtSe_(2)grain boundary with strong interfacial charge.The adsorption of TCNQ distinctly improves the band alignment at the PtSe_(2)grain boundaries.With the charge transfer between the grain boundary and TCNQ,the local charge is inhibited,and the band bending at the grain boundary is suppressed,as revealed by the scanning tunneling microscopy and spectroscopy(STM/S)results.Our finding provides an effective method for the advancement of the band alignment at the grain boundary by functional molecules,improving the electronic properties of 2D semiconductors for their future applications. | Yanhui Hou Ziqiang Xu Yan Shao Linlu Wu Zhongliu Liu Genyu Hu Wei Ji Jingsi Qiao Xu Wu Hong-Jun Gao Yeliang Wang | 2023 | Nano Research2023，16，2： | 0 |
| 4 | Band alignment and interlayer hybridization in monolayer organic/WSe_(2) heterojunction显示文摘Semiconducting heterojunctions(HJs),comprised of atomically thin transition metal dichalcogenides(TMDs),have shown great potentials in electronic and optoelectronic applications.Organic/TMD hybrid bilayers hold enhanced pumping efficiency of interfacial excitons,tunable electronic structures and optical properties,and other superior advantages to these inorganic HJs.Here,we report a direct probe of the interfacial electronic structures of a crystalline monolayer(ML)perylene-3,4,9,10-tetracarboxylic-dianhydride(PTCDA)/ML-WSe_(2) HJ using scanning tunneling microscopy,photoluminescence,and first-principle calculations.Strong PTCDAAA/Se_(2) interfacial interactions lead to appreciable hybridization of the WSe_(2) conduction band with PTCDA unoccupied states,accompanying with a significant amount of PTCDA-to-WSe_(2) charge transfer(by 0.06 e/PTCDA).A type-ll band alignment was directly determined with a valence band offset of-1.69 eV,and an apparent conduction band offset of-1.57 eV.Moreover,we found that the local stacking geometry at the HJ interface differentiates the hybridized interfacial states. | Yanping Guo Linlu Wu Jinghao Deng Linwei Zhou Wei Jiang Shuangzan Lu Da Huo Jiamin Ji Yusong Bai Xiaoyu Lin Shunping Zhang Hongxing Xu Wei Ji Chendong Zhang | 2022 | Nano Research2022，15，2： | 0 |
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