2017 Vol. 8, No. 7

Yu-Tao Loo and the development of neuropsychology in China
Yanyan Qian, Wei Chen, Shengjun Wen
2017, 8(7): 473-476. doi: 10.1007/s13238-017-0376-8
Physiological links of circadian clock and biological clock of aging
Fang Liu, Hung-Chun Chang
2017, 8(7): 477-488. doi: 10.1007/s13238-016-0366-2
Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold selfsustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.
Establishment and function of tissue-resident innate lymphoid cells in the skin
Jie Yang, Luming Zhao, Ming Xu, Na Xiong
2017, 8(7): 489-500. doi: 10.1007/s13238-017-0388-4
Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.
The development and function of dendritic cell populations and their regulation by miRNAs
Haibo Zhou, Li Wu
2017, 8(7): 501-513. doi: 10.1007/s13238-017-0398-2
Dendritic cells (DCs) are important immune cells linking innate and adaptive immune responses. DCs encounter various self and non-self antigens present in the environment and induce different types of antigen specific adaptive immune responses. DCs can be classified into lymphoid tissue-resident DCs, migratory DCs, non-lymphoid resident DCs, and monocyte derived DCs (moDCs). Recent work has also established that DCs consist of developmentally and functionally distinct subsets that differentially regulate T lymphocyte function. The development of different DC subsets has been found to be regulated by a network of different cytokines and transcriptional factors. Moreover, the response of DC is tightly regulated to maintain the homeostasis of immune system. MicroRNAs (miRNAs) are an important class of cellular regulators that modulate gene expression and thereby influence cell fate and function. In the immune system, miRNAs act at checkpoints during hematopoietic development and cell subset differentiation, they modulate effector cell function, and are implicated in the maintenance of homeostasis. DCs are also regulated by miRNAs. In the past decade, much progress has been made to understand the role of miRNAs in regulating the development and function of DCs. In this review, we summarize the origin and distribution of different mouse DC subsets in both lymphoid and non-lymphoid tissues. The DC subsets identified in human are also described. Recent progress on the function of miRNAs in the development and activation of DCs and their functional relevance to autoimmune diseases are discussed.
Research articles
Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation
Xiaojun Liu, Shuguang Jiang, Chongyun Fang, Hua Li, Xuhua Zhang, Fuqin Zhang, Carl H. June, Yangbing Zhao
2017, 8(7): 514-526. doi: 10.1007/s13238-017-0422-6
The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cellbased adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB). The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the coelectroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effective method for generating high-quality T cells for adoptive immunotherapy.
Shielding of the geomagnetic field reduces hydrogen peroxide production in human neuroblastoma cell and inhibits the activity of CuZn superoxide dismutase
Hai-tao Zhang, Zi-jian Zhang, Wei-chuan Mo, Ping-dong Hu, Hai-min Ding, Ying Liu, Qian Hua, Rong-qiao He
2017, 8(7): 527-537. doi: 10.1007/s13238-017-0403-9
Accumulative evidence has shown the adverse effects of a geomagnetic field shielded condition, so called a hypomagnetic field (HMF), on the metabolic processes and oxidative stress in animals and cells. However, the underlying mechanism remains unclear. In this study, we evaluate the role of HMF on the regulation of cellular reactive oxygen species (ROS) in human neuroblastoma SH-SY5Y cells. We found that HMF exposure led to ROS decrease, and that restoring the decrease by additional H2O2 rescued the HMF-enhanced cell proliferation. The measurements on ROS related indexes, including total anti-oxidant capacity, H2O2 and superoxide anion levels, and superoxide dismutase (SOD) activity and expression, indicated that the HMF reduced H2O2 production and inhibited the activity of CuZn-SOD. Moreover, the HMF accelerated the denaturation of CuZn-SOD as well as enhanced aggregation of CuZn-SOD protein, in vitro. Our findings indicate that CuZn-SOD is able to response to the HMF stress and suggest it a mediator of the HMF effect.
Synaptonemal complex protein 2 (SYCP2) mediates the association of the centromere with the synaptonemal complex
Jianrong Feng, Shijuan Fu, Xuan Cao, Hao Wu, Jing Lu, Ming Zeng, Lin Liu, Xue Yang, Yuequan Shen
2017, 8(7): 538-543. doi: 10.1007/s13238-016-0354-6
Identification of critical base pairs required for CTCF binding in motif M1 and M2
Wufeng Li, Liping Shang, Kaimeng Huang, Jiao Li, Zhibin Wang, Hongjie Yao
2017, 8(7): 544-549. doi: 10.1007/s13238-017-0387-5