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.

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.

Follicular helper T (TFH) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, naïve T cells are differentiating into TFH cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). TFH cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and TFH cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in TFH cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and TFH cell differentiation. TFH cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of TFH cells. The miR-17-92 cluster induces Bcl-6 and TFH cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T (TFR) cells are studied as thymus-derived CXCR5+PD-1+Foxp3+ Treg cells that play a significant role in limiting the GC response. Regulation of TFH cell differentiation and the GC reaction via miRNA and TFR cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect TFH cell differentiation, and the role of TFH cells in autoimmune diseases.

Purpose The purpose of this study is to evaluate prognostic factors, specifically age, at the time of surgery, for recurrence after bilateral lateral rectus recession (BLR) in patients with intermittent exotropia. Methods Medical records of 511 subjects who underwent BLR procedures between the ages of 3 and 10 years with more than 12 months of follow-up were retrospectively reviewed. Patients' surgical outcomes with a deviation of less than 10 prism diopters (PD) exotropia and less than 5 PD esotropia were defined as a success. Outcomes with more than 11 PD exotropia were designated as recurrences, and those with esotropia of more than 5 PD after 3 months of surgery were noted as overcorrection. Prognostic factors for recurrence were analyzed by multivariate logistic regression test. Results Of the 511 subjects, 371 had successful surgical outcomes and 129 had recurrences, whereas 11 were found to be overcorrected. Age at surgery and immediate postoperative alignment proved to be significant factors influencing a favorable outcome by multivariate logistic regression analysis (Po0.05). However, gender, photophobia, age at onset, spherical equivalent (SE) refractive error, astigmatism, SE anisometropia, and preoperative deviation size were not significantly predictive of success (P40.05). Conclusion In BLR procedures, increasing patient age at surgery was associated with lower recurrence rates.

Purpose To evaluate the prognostic factors, particularly age at the time of surgery, for recurrence after unilateral medial rectus resection and lateral rectus recession (R&R) procedures in patients with intermittent exotropia, or X(T). Methods Medical records of 489 subjects who received unilateral R&R procedures with more than 12 months of follow-up were reviewed. The patients' surgical outcomes with a deviation of less than 10 prism diopters (PD) of exotropia and less than 5 PD of esotropia were defined as a success. Outcomes with more than 11 PD of exotropia were designated as recurrences, and those with esotropia of more than 5 PD after 3 months of operation were noted as overcorrection. The prognostic factors for recurrence were analyzed by the multivariate logistic regression test. Results Of the 489 subjects, 209 had successful surgical outcomes and 280 had recurrences, whereas overcorrection was not found. Mean age at operation was 8.9 ± 6.5 years, mean preoperative distant X(T) size was 32.9 ± 6.0 PD, and mean follow-up period was 27.5 ± 17.9 months. On the basis of the survival analysis in which survival represented time of recurrence, the mean duration was 31.2±1.7months. Age at onset, age at surgery, and immediate postoperative alignment proved to be significant factors influencing a favorable outcome by multivariate logistic regression analysis (Po0.05). However, gender, family history, and preoperative deviation size were not significantly predictive of success (P40.05). ConclusionIn unilateral R&R procedures, increasing patient age at the time of surgery was associated with lower recurrence rates. Recurrence rates also increased with the immediate postoperative angle and with the postoperative angle of deviation at 1, 3, 6, and 12 months.

Anterior segment optical coherence tomography (AS-OCT) was recently developed and has become a crucial tool in clinical practice. AS-OCT is a noncontact imaging device that provides the detailed structure of the anterior part of the eyes. In this review, the author will discuss the various clinical applications of AS-OCT, such as the normal findings, tear meniscus measurement, ocular surface disease (e.g., pterygium, pinguecula, and scleromalacia), architectural analysis after cataract surgery, post-LASIK keratectasia, Descemet's membrane detachment, evaluation of corneal graft after keratoplasty, corneal deposits (corneal dystrophies and corneal verticillata), keratitis, anterior segment tumors, and glaucoma evaluation (angle assessment, morphological analysis of the filtering bleb after trabeculectomy, or glaucoma drainage device implantation surgery). The author also presents some interesting cases demonstrated via AS-OCT.

Although trabeculectomy for XFG had success rates similar to POAG at 1 year, XFG showed poorer long-term IOP control from 2 years postoperatively. This study indicates that it is more difficult to achieve long-term low target IOP control in eyes with XFG than in eyes with POAG after trabeculectomy with mitomycin-C.