T cells are the central mediators of both humoral and cellular adaptive immune responses. Highly specific receptor-mediated clonal selection and expansion of T cells assure antigen-specific immunity. ...In addition, encounters with cognate antigens generate immunological memory, the capacity for long-term, antigen-specific immunity against previously encountered pathogens. However, T-cell receptor (TCR)-independent activation, termed "bystander activation", has also been found. Bystander-activated T cells can respond rapidly and secrete effector cytokines even in the absence of antigen stimulation. Recent studies have rehighlighted the importance of antigen-independent bystander activation of CD4
T cells in infection clearance and autoimmune pathogenesis, suggesting the existence of a distinct innate-like immunological function performed by conventional T cells. In this review, we discuss the inflammatory mediators that activate bystander CD4
T cells and the potential physiological roles of these cells during infection, autoimmunity, and cancer.
Cancer immunotherapies, including adoptive T cell transfer and immune checkpoint blockades, have recently shown considerable success in cancer treatment. Nevertheless, transferred T cells often ...become exhausted because of the immunosuppressive tumor microenvironment. Immune checkpoint blockades, in contrast, can reinvigorate the exhausted T cells; however, the therapeutic efficacy is modest in 70–80% of patients. To address some of the challenges faced by the current cancer treatments, here T‐cell‐membrane‐coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. Similar to cytotoxic T cells, TCMNPs can be targeted at tumors via T‐cell‐membrane‐originated proteins and kill cancer cells by releasing anticancer molecules and inducing Fas‐ligand‐mediated apoptosis. Unlike cytotoxic T cells, TCMNPs are resistant to immunosuppressive molecules (e.g., transforming growth factor‐β1 (TGF‐β1)) and programmed death‐ligand 1 (PD‐L1) of cancer cells by scavenging TGF‐β1 and PD‐L1. Indeed, TCMNPs exhibit higher therapeutic efficacy than an immune checkpoint blockade in melanoma treatment. Furthermore, the anti‐tumoral actions of TCMNPs are also demonstrated in the treatment of lung cancer in an antigen‐nonspecific manner. Taken together, TCMNPs have a potential to improve the current cancer immunotherapy.
T‐cell‐membrane‐coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. The TCMNPs can be targeted at tumors and kill cancer cells while being resistant to the pro‐tumoral factors in the tumor microenvironment. Indeed, the TCMNPs exhibit a higher therapeutic efficacy than current cancer treatments based on immune checkpoint blockade, and they are effective for the treatment of various tumors.
T cells generate antigen-specific immune responses to their cognate antigen as a hallmark of adaptive immunity. Despite the importance of antigen-specific T cells, here we show that antigen ...non-related, bystander memory-like CD4
T cells also significantly contribute to autoimmune pathogenesis. Transcriptome analysis demonstrates that interleukin (IL)-1β- and IL-23-prime T cells that express pathogenic T
17 signature genes such as RORγt, CCR6, and granulocyte macrophage colony-stimulating factor (GM-CSF). Importantly, when co-transferred with myelin-specific 2D2 TCR-transgenic naive T cells, unrelated OT-II TCR-transgenic memory-like T
17 cells infiltrate the spinal cord and produce IL-17A, interferon (IFN)-γ, and GM-CSF, increasing the susceptibility of the recipients to experimental autoimmune encephalomyelitis in an IL-1 receptor-dependent manner. In humans, IL-1R1
memory CD4
T cells are major producers of IL-17A and IFN-γ in response to IL-1β and IL-23. Collectively, our findings reveal the innate-like pathogenic function of antigen non-related memory CD4
T cells, which contributes to the development of autoimmune diseases.
The nuclear factor of activated T cells (NFAT) family of transcription factors, which includes NFAT1, NFAT2, and NFAT4, are well-known to play important roles in T cell activation. Most of NFAT ...proteins are controlled by calcium influx upon T cell receptor and costimulatory signaling results increase of IL-2 and IL-2 receptor. NFAT3 however is not shown to be expressed in T cells and NFAT5 has not much highlighted in T cell functions yet. Recent studies demonstrate that the NFAT family proteins involve in function of lineage-specific transcription factors during differentiation of T helper 1 (Th1), Th2, Th17, regulatory T (Treg), and follicular helper T cells (Tfh). They have been studied to make physical interaction with the other transcription factors like GATA3 or Foxp3 and they also regulate Th cell signature gene expressions by direct binding on promotor region of target genes. From last decades, NFAT functions in T cells have been targeted to develop immune modulatory drugs for controlling T cell immunity in autoimmune diseases like cyclosporine A, FK506, etc. Due to their undesirable side defects, only limited application is available in human diseases. This review focuses on the recent advances in development of NFAT targeting drug as well as our understanding of each NFAT family protein in T cell biology. We also discuss updated detail molecular mechanism of NFAT functions in T cells, which would lead us to suggest an idea for developing specific NFAT inhibitors as a therapeutic drug for autoimmune diseases.
Abstract
Considering their superior charge-transfer characteristics, easy tenability of energy levels, and low production cost, organic semiconductors are ideal for photoelectrochemical (PEC) ...hydrogen production. However, organic-semiconductor-based photoelectrodes have not been extensively explored for PEC water-splitting because of their low stability in water. Herein, we report high-performance and stable organic-semiconductors photoanodes consisting of
p
-type polymers and
n
-type non-fullerene materials, which is passivated using nickel foils, GaIn eutectic, and layered double hydroxides as model materials. We achieve a photocurrent density of 15.1 mA cm
−2
at 1.23 V vs. reversible hydrogen electrode (RHE) with an onset potential of 0.55 V vs. RHE and a record high half-cell solar-to-hydrogen conversion efficiency of 4.33% under AM 1.5 G solar simulated light. After conducting the stability test at 1.3 V vs. RHE for 10 h, 90% of the initial photocurrent density are retained, whereas the photoactive layer without passivation lost its activity within a few minutes.
Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given ...the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism.
Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To ...modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN-γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.
Chitinase-3-like-1 (Chi3l1) is known to play a significant role in the pathogenesis of Type 2 inflammation and cancer. However, the function of Chi3l1 in T cell and its clinical implications are ...largely unknown. Here we show that Chi3l1 expression was increased in activated T cells, especially in Th2 cells. In addition, Chi3l1-deficient T cells are hyper-responsive to TcR stimulation and are prone to differentiating into Th1 cells. Chi3l1-deficient Th1 cells show increased expression of anti-tumor immunity genes and decreased Th1 negative regulators. Deletion of Chi3l1 in T cells in mice show reduced melanoma lung metastasis with increased IFNγ and TNFα-producing T cells in the lung. Furthermore, silencing of Chi3l1 expression in the lung using peptide-siRNA complex (dNP2-siChi3l1) efficiently inhibit lung metastasis with enhanced Th1 and CTL responses. Collectively, this study demonstrates Chi3l1 is a regulator of Th1 and CTL which could be a therapeutic target to enhance anti-tumor immunity.
The smartphone has many attractive attributes and characteristics that could make it highly addictive, particularly in adolescents. The purpose of this study was to examine the prevalence of young ...adolescents in risk of smartphone addiction and the psychological factors associated with smartphone addiction. Four hundred ninety middle school students completed a self-questionnaire measuring levels of smartphone addiction, behavioral and emotional problems, self-esteem, anxiety, and adolescent-parent communication. One hundred twenty-eight (26.61%) adolescents were in high risk of smartphone addiction. This latter group showed significantly more severe levels of behavioral and emotional problems, lower self-esteem, and poorer quality of communication with their parents. Multiple regression analysis revealed that the severity of smartphone addiction is significantly associated with aggressive behavior (β = .593, t = 3.825) and self-esteem (β = −.305, t = −2.258). Further exploratory and confirmatory studies should consider different sites, demographics, technological mobile devices, platforms, and applications.
Alba (Acetylation lowers binding affinity) proteins are an ancient family of nucleic acid-binding proteins that function in gene regulation, RNA metabolism, mRNA translatability, developmental ...processes, and stress adaptation. However, comprehensive bioinformatics analysis on the Alba gene family of Solanum lycopersicum has not been reported previously.
In the present study, we undertook the first comprehensive genome-wide characterization of the Alba gene family in tomato (Solanum lycopersicum L.). We identified eight tomato Alba genes, which were classified into two groups: genes containing a single Alba domain and genes with a generic Alba domain and RGG/RG repeat motifs. Cis-regulatory elements and target sites for miRNAs, which function in plant development and stress responses, were prevalent in SlAlba genes. To explore the structure-function relationships of tomato Alba proteins, we predicted their 3D structures, highlighting their likely interactions with several putative ligands. Confocal microscopy revealed that SlAlba-GFP fusion proteins were localized to the nucleus and cytoplasm, consistent with putative roles in various signalling cascades. Expression profiling revealed the differential expression patterns of most SlAlba genes across diverse organs. SlAlba1 and SlAlba2 were predominantly expressed in flowers, whereas SlAlba5 expression peaked in 1 cm-diameter fruits. The SlAlba genes were differentially expressed (up- or downregulated) in response to different abiotic stresses. All but one of these genes were induced by abscisic acid treatment, pointing to their possible regulatory roles in stress tolerance via an abscisic acid-dependent pathway. Furthermore, co-expression of SlAlba genes with multiple genes related to several metabolic pathways spotlighted their crucial roles in various biological processes and signalling.
Our characterization of SlAlba genes should facilitate the discovery of additional genes associated with organ and fruit development as well as abiotic stress adaptation in tomato.
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