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.
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