No abstract

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.

Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here we identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood–brain barrier. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood–brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS.

[Purpose] To determine the effect of dual-task training with cognitive tasks on cognitive and walking ability after stroke. [Subjects and Methods] Twenty patients diagnosed with stroke participated in this study. All participants were receiving a traditional rehabilitation program 5 days a week. Dual-task and single-task training were additionally performed for 4 weeks, 3 days a week. The Stroop test, Timed Up and Go (TUG) test, 10-Meter Walk Test (10MWT), and Figure-of-8 Walk Test (F8WT) were used to measure cognitive and walking abilities and were evaluated 3 times (before and after training and at the 2-week follow-up). [Results] Dual-task training improved cognitive and walking abilities, and dual-task training subjects’ performance was better than single-task training subjects’ performance. In addition, these training benefits were maintained for 2 weeks. [Conclusion] Dual-task training improves cognitive and walking abilities of patients with stroke.

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 TΗ17 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 TH17 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-1R1high 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.

[Purpose] The purpose of this study was to examine the effects on stroke patients of trunk stabilization exercise on different support surfaces. [Subjects and Methods] Sixteen stroke patients with onset of stroke six months earlier or longer were randomly and equally assigned to group I (exercise performed on a stable support surface) and group II (exercise performed on an unstable support surface). The two groups conducted the trunk stabilization exercises on the respective support surfaces, in addition to existing rehabilitation exercises five times per week for 12 weeks. Changes in the cross-sectional area (CSA) of the muscles were examined using computed tomography (CT), and changes in the balance ability were assessed using a measuring system and the trunk impairment scale (TIS). [Results] In group I, there was a significant increase in the CSA of the mulifidus muscle on the side contralateral to the brain lesion and in the paravertebral and multifidus muscles on the side ipsilateral to the brain lesion. In group II, there was a significant increase in the CSA of the paravertebral and multifidus muscles on the side contralateral to the brain lesion and on the side ipsilateral to the brain lesion. In terms of changes in balance ability, the sway path (SP) and TIS significantly improved in group I, and the SP, sway area (SA), and TIS significantly improved in group II . [Conclusion] Exercise on the unstable support surface enhanced the size of the cross-sectional area of the trunk muscles and balance ability significantly more than exercise on the stable support surface.

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.

Weakening of trunk muscles in stroke patients hinders functional ability, safety and balance. To confirm whether strengthening trunk muscles could facilitate rehabilitation of stroke patients, we investigated the effectiveness of sling exercise therapy (SET) using closed kinetic chain exercises to activate trunk muscles and improve balance in stroke patients. [Subjects and Methods] Twenty stroke patients with chronic hemiplegia were equally divided into 2 groups, a SET group and a control group that performed regular exercises on a mat with the assistance of a table. Patients in both groups exercised for 30 min, three times per week for 4 weeks. Trunk muscle activity was measured using surface electromyography, whereas balance was measured using the Berg Balance Scale, Frailty and Injuries Cooperative Studies of Intervention Technique, Timed Up & Go test, and BioRescue before and after the 4-week experimental period. [Results] Trunk muscle activity and balance before and after intervention in both groups were significantly different. However, no significant differences were observed between the 2 groups. [Conclusion] Although SET was not more effective than regular exercise, significant improvement was observed before and after SET. Therefore, SET can be considered effective in strengthening trunk muscles in stroke patients with chronic hemiplegia.