The Neuroprotective Effect of Therapeutic Hypothermia in Cognitive Impairment of an Ischemia/Reperfusion Injury Mouse Model.

Background and Objectives: Therapeutic hypothermia (TH) shows promise as an approach with neuroprotective effects, capable of reducing secondary brain damage and intracranial pressure following successful mechanical thrombectomy in the acute phase. However, its effect on cognitive impairment remains unclear. This study investigated whether TH can improve cognitive impairment in a mouse model of transient middle cerebral artery occlusion followed by reperfusion (tMCAO/R). Materials and Methods: Nine-week-old C57BL/6N mice (male) were randomly assigned to three groups: sham, tMCAO/R, and tMCAO/R with TH. Cognitive function was assessed 1 month after model induction using the Y-maze test, and regional cerebral glucose metabolism was measured through positron emission tomography with fluorine-18 fluorodeoxyglucose. Results: tMCAO/R induced cognitive impairment, which showed improvement with TH. The TH group exhibited a significant recovery in cerebral glucose metabolism in the thalamus compared to the tMCAO/R group. Conclusions: These findings indicate that TH may hold promise as a therapeutic strategy for alleviating ischemia/reperfusion-induced cognitive impairment.

Controlling spatial distribution of functional lipids in a supported lipid bilayer prepared from vesicles.

Conjugating biomolecules, such as antibodies, to bioconjugate moieties on lipid surfaces is a powerful tool for engineering the surface of diverse biomaterials, including cells and nanoparticles. We developed supported lipid bilayers (SLBs) presenting well-defined spatial distributions of functional moieties as models for precisely engineered functional biomolecular-lipid surfaces. We used quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM) to determine how vesicles containing a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[azido(polyethylene glycol)-2000] (DSPE-PEG-N3) form SLBs as a function of the lipid phase transition temperature (Tm). Above the DPPC Tm, DPPC/DSPE-PEG-N3 vesicles form SLBs with functional azide moieties on SiO2 substrates via vesicle fusion. Below this Tm, DPPC/DSPE-PEG-N3 vesicles attach to SiO2 intact. Intact DPPC/DSPE-PEG-N3 vesicles on the SiO2 surfaces fuse and rupture to form SLBs when temperature is brought above the DPPC Tm. AFM studies show uniform and complete DPPC/DSPE-PEG-N3 SLB coverage of SiO2 surfaces for different DSPE-PEG-N3 concentrations. As the DSPE-PEG-N3 concentration increases from 0.01 to 6 mol%, the intermolecular spacing of DSPE-PEG-N3 in the SLBs decreases from 4.6 to 1.0 nm. The PEG moiety undergoes a mushroom to brush transition as DSPE-PEG-N3 concentration varies from 0.1 to 2.0 mol%. Via copper-free click reaction, IgG was conjugated to SLB surfaces with 4.6 nm or 1.3 nm inter-DSPE-PEG-N3 spacing. QCM-D and AFM data show; 1) uniform and complete IgG layers of similar mass and thickness on the two types of SLB; 2) a higher-viscosity/less rigid IgG layer on the SLB with 4.6 nm inter-DSPE-PEG-N3 spacing. Our studies provide a blueprint for SLBs modeling spatial control of functional macromolecules on lipid surfaces, including surfaces of lipid nanoparticles and cells.

Peptides as multifunctional players in cancer therapy.

Peptides exhibit lower affinity and a shorter half-life in the body than antibodies. Conversely, peptides demonstrate higher efficiency in tissue penetration and cell internalization than antibodies. Regardless of the pros and cons of peptides, they have been used as tumor-homing ligands for delivering carriers (such as nanoparticles, extracellular vesicles, and cells) and cargoes (such as cytotoxic peptides and radioisotopes) to tumors. Additionally, tumor-homing peptides have been conjugated with cargoes such as small-molecule or chemotherapeutic drugs via linkers to synthesize peptide-drug conjugates. In addition, peptides selectively bind to cell surface receptors and proteins, such as immune checkpoints, receptor kinases, and hormone receptors, subsequently blocking their biological activity or serving as hormone analogs. Furthermore, peptides internalized into cells bind to intracellular proteins and interfere with protein-protein interactions. Thus, peptides demonstrate great application potential as multifunctional players in cancer therapy.

The rise of ChatGPT: Exploring its potential in medical education.

The integration of artificial intelligence (AI) into medical education has the potential to revolutionize the way students learn about biomedical sciences. Large language models, such as ChatGPT, can serve as virtual teaching assistants, providing students with detailed and relevant information and perhaps eventually interactive simulations. ChatGPT has the potential to increase student engagement and enhance student learning, though research is needed to confirm this. The challenges and limitations of ChatGPT must also be considered, including ethical issues and potentially harmful effects. It is crucial for medical educators to keep pace with technology's rapidly changing landscape and consider the implications for curriculum design, assessment strategies, and teaching methods. Continued research and evaluation are necessary to ensure the optimal integration of AI-based learning tools into medical education.

An Image Turing Test on Realistic Gastroscopy Images Generated by Using the Progressive Growing of Generative Adversarial Networks.

Generative adversarial networks (GAN) in medicine are valuable techniques for augmenting unbalanced rare data, anomaly detection, and avoiding patient privacy issues. However, there were limits to generating high-quality endoscopic images with various characteristics, such as peristalsis, viewpoints, light sources, and mucous patterns. This study used the progressive growing of GAN (PGGAN) within the normal distribution dataset to confirm the ability to generate high-quality gastrointestinal images and investigated what barriers PGGAN has to generate endoscopic images. We trained the PGGAN with 107,060 gastroscopy images from 4165 normal patients to generate highly realistic 5122 pixel-sized images. For the evaluation, visual Turing tests were conducted on 100 real and 100 synthetic images to distinguish the authenticity of images by 19 endoscopists. The endoscopists were divided into three groups based on their years of clinical experience for subgroup analysis. The overall accuracy, sensitivity, and specificity of the 19 endoscopist groups were 61.3%, 70.3%, and 52.4%, respectively. The mean accuracy of the three endoscopist groups was 62.4 [Group I], 59.8 [Group II], and 59.1% [Group III], which was not considered a significant difference. There were no statistically significant differences in the location of the stomach. However, the real images with the anatomical landmark pylorus had higher detection sensitivity. The images generated by PGGAN showed highly realistic depictions that were difficult to distinguish, regardless of their expertise as endoscopists. However, it was necessary to establish GANs that could better represent the rugal folds and mucous membrane texture.

Bioinformatic analysis of the obesity paradox and possible associated factors in colorectal cancer using TCGA cohorts.

Colorectal cancer (CRC) is a common malignancy worldwide and the second leading cause of cancer-related deaths. Obesity is an important determinant of CRC incidence; however, obese patients have also shown better long-term survival than non-obese patients, suggesting that the development and progression of CRC are associated with different mechanisms. This study compares the expression of genes, tumor-infiltrating immune cells, and intestinal microbiota between high- and low-body mass index (BMI) patients at the time of CRC diagnosis. The results revealed that high-BMI patients with CRC have better prognosis, higher levels of resting CD4+ T cells, lower levels of T follicular helper cells, and different levels of intratumoral microbiota than low-BMI patients. Our study highlights that tumor-infiltrating immune cells and intratumoral microbe diversity are major features of the obesity paradox in CRC.

The lysosome as a novel therapeutic target of EGFR-mediated tumor inflammation.

EGFR-mediated tumors have been targeted to overcome several different malignant cancers. EGFR overexpression and mutations are directly related to the malignancy, which makes the therapy more complicated. One reason for the malignancy is the induction of AP1 followed by inflammation via IL-6 secretion. Current therapeutic strategies to overcome EGFR-mediated tumors are tyrosine kinase inhibitors (TKIs), anti-EGFR monoclonal antibodies, and the combination of these two agents with classic chemotherapy or immune checkpoint inhibitors (ICIs). Although the strategies are straightforward and have shown promising efficacy in several studies, there are still hurdles to overcoming the adverse effects and limited efficacy. This study reviews the current therapeutic strategies to target EGFR family members, how they work, and their effects and limitations. We also suggest developing novel strategies to target EGFR-mediated tumors in a novel approach. A lysosome is the main custodial staff to discard unwanted amounts of EGFR and other receptor tyrosine kinase molecules. Targeting this organelle may be a new approach to overcoming EGFR-mediated cancers.

Callicarpa dichotoma Leaf Extract Alleviates Atopic Dermatitis through the Suppression of T Cells and Keratinocytes Activation.

Atopic dermatitis (AD) is a highly recurrent chronic inflammatory skin disease, characterized by severe itching, immune imbalance, and skin barrier dysfunction. Damage to the skin barrier function is known to be the main cause of Th1/Th2 immune imbalance, due to the Th2-mediated immune response, and pro-inflammatory cytokines, including IL-4, IL-5, IL-13 and IL-31 and it plays an important role in further eliciting the environment of AD through stimulation. Currently, the most widely used drugs for the treatment of AD are corticosteroids, antihistamines and immunosuppressants (used by more than 60% of patients), which are reported to exhibit various side effects when taken for a long time. Therefore, interest in the physiological activity of safer plant-derived natural extracts is increasing. Callicarpa dichotoma is traditionally used in oriental medicine for bruises, habitual pain, gastric and postpartum hemorrhage. Recent studies have reported that it exhibits antioxidant anti-inflammatory and anti-hepatotoxic activity, but the role and activity of C. dichotoma in AD have not yet been studied. Therefore, in this study, the new physiological activity of C. dichotoma in the AD environment was investigated, suggesting its potential as a natural therapeutic agent.

Exceptional Repositioning of Dog Dewormer: Fenbendazole Fever.

Fenbendazole (FZ) is a benzimidazole carbamate drug with broad-spectrum antiparasitic activity in humans and animals. The mechanism of action of FZ is associated with microtubular polymerization inhibition and glucose uptake blockade resulting in reduced glycogen stores and decreased ATP formation in the adult stages of susceptible parasites. A completely cured case of lung cancer became known globally and greatly influenced the cancer community in South Korea. Desperate Korean patients with cancer began self-administering FZ without their physician's knowledge, which interfered with the outcome of the cancer treatment planned by their oncologists. On the basis of presented evidence, this review provides valuable information from PubMed, Naver, Google Scholar, and Social Network Services (SNS) on the effects of FZ in a broad range of preclinical studies on cancer. In addition, we suggest investigating the self-administration of products, including supplements, herbs, or bioactive compounds, by patients to circumvent waiting for long and costly FZ clinical trials.

Oral administration of Helianthus annuus leaf extract ameliorates atopic dermatitis by modulation of T cell activity in vivo.

BACKGROUND: Atopic dermatitis (AD) is multifactorial disease that is highly involved in the activity of T cells from the skin lesion. Seeds of Helianthus annuus extract have been traditionally used as anti-inflammatory reagent but few studies have been reported on leaf of H. annuus that are discarded uselessly as an immunomodulator. PURPOSE: Therefore, here, the regulatory effect of Helianthus annuus extract (HAE) on AD via suppression of T cell activity was investigated. METHODS: The efficacy of HAE was evaluated in T cells stimulated with CD3/CD28 antibody and PMA/A23187. And demonstration of the alleviating effect of HAE on AD in the ears of Balb/c female mice stimulated with mite extract and DNCB. RESULTS: Pre-treatment with HAE abrogates IL-2 production from activated T cells. It was also found that HAE suppresses the expression of surface molecules in activated T cells. Cell viability results demonstrated that HAE is not associated with cytotoxicity in resting and activated T cells. Besides, we exhibited that regulated phosphorylation of MAPK through TAK1-IKKα-NFκB by pre-treatment with HAE leads to the suppressive effect of HAE on T cell activation. Oral administration of HAE attenuates manifestations of AD including reduced thickness of dermis and epidermis, decreased IgE level in serum, and declined mRNA levels of atopic cytokines on ear tissues. The ameliorative effect of HAE on AD was found to be associated with suppressed activity of T cells from draining lymph nodes. CONCLUSION: Therefore, our results provide that HAE alleviates AD symptoms via modulation of T cell activity. In addition, these results suggest the immunomodulatory effect of HAE on T-cell mediated diseases.

Ameliorative Effect of Citropten Isolated from Citrusaurantifolia Peel Extract as a Modulator of T Cell and Intestinal Epithelial Cell Activity in DSS-Induced Colitis.

Citropten is a coumarin that is mainly found in fruits of Rutaceae trees, but its anti-inflammatory activities in colitis is still unknown. In this study, we investigated its attenuating effect of citropten isolated from Citrus aurantifolia extract on DSS-induced colitis through the modulation of the activity of T cells and intestinal epithelial cells. We found that pre-treatment with citropten downregulates the activity of T cells and intestinal epithelial cells without a negative effect on the viability of Jurkat and HT-29 cells. The results from the Western blot analysis revealed that pre-treatment with citropten reduces the NFκB and MAPK signaling pathway in activated T cells and intestinal epithelial cells. We elucidated that the oral administration of citropten alleviates the colonic inflammation and activity of effector T cells in DSS-induced colitis by measuring changes in body weight, histological scoring from H&E-stained sections, mRNA levels of pro-inflammatory cytokines and the phosphorylation level of the MAPK signaling pathway.

A Load-Insensitive Hybrid LSK Back Telemetry System With Slope-Based Demodulation for Inductively Powered Biomedical Devices.

This paper presents a hybrid load-shift keying (LSK) modulation for a load-insensitive back telemetry system to realize near-constant voltage changes in a primary coil (L1) against a wide range of load variations. The hybrid-LSK-enabled full-wave rectifier enables the sequential combination of open- and short-coil functions for hybrid-LSK modulation in addition to wireless power conversion operation. Load-insensitive L1 voltage changes can be demodulated using the proposed slope- based demodulator, which utilizes the threshold slope of L1 voltage changes over the back data pulse width, enabling robust data recovery regardless of the load conditions. The 0.56-mm2 0.18-µm standard CMOS hybrid-LSK prototype demonstrated that the variation of L1 voltage changes could be minimized to 60 mV under load changes between 50 Ω and 50 kΩ at coil separation distance of 10 mm, achieving 88.2% reduction compared to the conventional short-coil LSK with 510 mV variation. The proposed back telemetry system also achieved a bit error rate (BER) of < 9.1 × 10-10 under load ranges from 50 Ω to 50 kΩ and data rate of 1 Mbps, ensuring reliable back data recovery against load variations.

A Simple Method to Locate the Master Knot of Henry Using the Correlation between the Flexor Tendon Length Parameter and the Foot Length.

The precise location of the Master Knot of Henry (MKH) has important clinical significance, but its anatomical definition has not been agreed upon. The purpose of this study is to present a linear regression equation for predicting length variables based on foot length, by evaluating the correlation of length variables related to flexor hallucis longus (FHL) and flexor digitorum longus (FDL), with respect to the location of the MKH. A total of 95 limbs were dissected from 48 adult cadavers, and were fixed in formalin. Measurements were made for the length parameter, with reference to the landmark. The relevance between length variables was analyzed through simple correlation analysis and linear regression analysis. The foot length was 213.69 ± 17.53 mm, MKH-great toe distal phalanx was 140.16 ± 14.69 mm, MKH-FHL insertion was 124.55 ± 13.46 mm, MKH-little toe distal phalanx was 121.79 ± 13.41 mm, MKH-FDL little toe insertion was 109.07 ± 14.16 mm, and the FHL-FDL angle was 33.15 ± 5.39. The correlation coefficient between all the length variables for foot length showed a high positive correlation. We derived a regression equation that can predict the length of each variable. This regression formula is considered to be highly useful because it can estimate the positional relationship of the MKH relatively simply.

Clinical Value of EZH2 in Hepatocellular Carcinoma and Its Potential for Target Therapy.

Background and objectives: EZH2 is overexpressed in hepatocellular carcinoma (HCC) and is correlated with poor prognosis. However, its clinical significance and molecular mechanism have not been studied in HCC. In this study, clinical and prognostic values of EZH2 was studied using Total Cancer Genome Atlas (TCGA) data and then, these data were confirmed in Huh1 and HepG2 cell lines. Materials and Methods: We used the TCGA database from cBioPortal. In addition, we analyzed EZH2 mRNA levels in HCC cell lines and its correlation with STAT3 and EZH2. Results: According to TCGA, EZH2 had a prognostic value in various cancers, especially in HCC. Furthermore, EZH2 in HCC was correlated with N stage (p = 0.045) and alpha-fetoprotein (AFP) > 20 ng/mL (p < 0.01). However, a negative association between EZH2 and age (p = 0.027) was found. The overall survival result of HCC was significantly poorer in patients with high EZH2 expression. In addition, the recurrence rate was also significantly higher in patients with high expression of EZH2 than those with low expression (χ2 = 16.10, p < 0.001). EZH2 expression was negatively correlated with STAT3 expression among EZH2-associated genes (R = -0.163, p = 0.002). EZH2 expression level was down-regulated to 50% or less compared to the control group treated negative siRNA. MTT assays showed that EZH2-siRNA affected on the viability of HCC cell line significantly. Conclusions: In conclusion, the overexpression of EZH2 was an independent biomarker for poor outcomes of HCC. However, more in vivo studies are required to identify the downstream target genes in HCC to improve our understanding of the biological role of EZH2 in HCC.

Effect on Osteoclast Differentiation and ER Stress Downregulation by Amygdalin and RANKL Binding Interaction.

Bone diseases such as osteoporosis are the result of osteoclast over-activation. There are many therapeutic agents from natural compounds inhibiting the formation of osteoclast that have been reported and are continuously being interested. Amygdalin (AD) is isolated from seeds of Prunus armeniaca L. which has many pharmaceutical effects; however, the effect of AD on osteoclast formation and function remains unknown. Therefore, the underlying mechanism of AD on RANKL-induced osteoclast in RAW 264.7 cells was investigated. Molecular docking simulation revealed that AD can bind to the active sites of RANKL with negative binding affinities. Through TRAP activity, bone resorption, and migration, AD effectively inhibited osteoclast differentiation and function. Expression of transcription factors, such as NFATc1, c-fos, and osteospecific genes (including dcstamp, acp5, ATP6v0d2, and ctsk results) showed an osteoclast differentiated inhibitory effect by AD treatment. In addition, RANKL-induced activation of MAPK, ER stress, and ROS levels in RANKL-induced osteoclast was significantly inhibited while antioxidant enzymes were recovered in the presence of AD. These results suggest that AD may be a potential candidate derived from natural sources for the treatment of osteoclast bone-related diseases.

Toward the biological model of the hippocampus as the successor representation agent.

The hippocampus is an essential brain region for spatial memory and learning. Recently, a theoretical model of the hippocampus based on temporal difference (TD) learning has been published. Inspired by the successor representation (SR) learning algorithms, which decompose value function of TD learning into reward and state transition, they argued that the rate of firing of CA1 place cells in the hippocampus represents the probability of state transition. This theory, called predictive map theory, claims that the hippocampus representing space learns the probability of transition from the current state to the future state. The neural correlates of expecting the future state are the firing rates of the CA1 place cells. This explanation is plausible for the results recorded in behavioral experiments, but it is lacking the neurobiological implications. Modifying the SR learning algorithm added biological implications to the predictive map theory. Similar with the simultaneous needs of information of the current and future state in the SR learning algorithm, the CA1 place cells receive two inputs from CA3 and entorhinal cortex. Mathematical transformation showed that the SR learning algorithm is equivalent to the heterosynaptic plasticity rule. The heterosynaptic plasticity phenomena in CA1 were discussed and compared with the modified SR update rule. This study attempted to interpret the TD algorithm as the neurobiological mechanism occurring in place learning, and to integrate the neuroscience and artificial intelligence approaches in the field.

IL-27-producing B-1a cells suppress neuroinflammation and CNS autoimmune diseases.

Regulatory B cells (Breg cells) that secrete IL-10 or IL-35 (i35-Breg) play key roles in regulating immunity in tumor microenvironment or during autoimmune and infectious diseases. Thus, loss of Breg function is implicated in development of autoimmune diseases while aberrant elevation of Breg prevents sterilizing immunity, exacerbates infectious diseases, and promotes cancer metastasis. Breg cells identified thus far are largely antigen-specific and derive mainly from B2-lymphocyte lineage. Here, we describe an innate-like IL-27-producing natural regulatory B-1a cell (i27-Breg) in peritoneal cavity and human umbilical cord blood. i27-Bregs accumulate in CNS and lymphoid tissues during neuroinflammation and confers protection against CNS autoimmune disease. i27-Breg immunotherapy ameliorated encephalomyelitis and uveitis through up-regulation of inhibitory receptors (Lag3, PD-1), suppression of Th17/Th1 responses, and propagating inhibitory signals that convert conventional B cells to regulatory lymphocytes that secrete IL-10 and/or IL-35 in eye, brain, or spinal cord. Furthermore, i27-Breg proliferates in vivo and sustains IL-27 secretion in CNS and lymphoid tissues, a therapeutic advantage over administering biologics (IL-10, IL-35) that are rapidly cleared in vivo. Mutant mice lacking irf4 in B cells exhibit exaggerated increase of i27-Bregs with few i35-Bregs, while mice with loss of irf8 in B cells have abundance of i35-Bregs but defective in generating i27-Bregs, identifying IRF8/BATF and IRF4/BATF axis in skewing B cell differentiation toward i27-Breg and i35-Breg developmental programs, respectively. Consistent with its developmental origin, disease suppression by innate i27-Bregs is neither antigen-specific nor disease-specific, suggesting that i27-Breg would be effective immunotherapy for a wide spectrum of autoimmune diseases.

Topography and Anatomical Variations of the Axillary Artery.

Knowledge of anatomical variations of the limb's main arteries is significant for the clinicians. Thus, this study is aimed at examining the branching pattern and anatomical variations of the axillary artery. We conducted research on 59 upper limbs of adult human donated cadavers. All axillary artery branches' origins were assessed, and the correlations between points of origins and variations of specific branches were evaluated. The average length of the axillary artery was found to be 11.22 cm, and this length was defined as reference line. Based on this reference line, the first, second, and third parts were 37.56%, 39%, and 30.05%, respectively. The STA was originated from 25.11%. The TAA and LTA were 42.67% and 54.82%, respectively. The SSA, ACHA, and PCHA were 64.72%, 83.89%, and 84.53%, respectively. The origin of LTA was correlated with that of SSA (R = 0.473, P < 0.05) and AHCA (R = 0.307, P < 0.05), respectively. And there was a positive correlation between AHCA and PHCA (R = 0.705, P < 0.05). The number of branches ranged from 3~6, and 9 types were shown. The most frequent branching pattern was common origin of the LTA and SSA (22/59). And AHCA and PHCA were originated together in 19 cases, and both patterns were combined in 12 cases. TTA and LTA branched together in 9 cases, and common trunk for the SSA, PHCA, and AHCA was found in 2 cases. According to this pattern, the origin of LTA and PCHA was significantly different. This information is particularly useful for surgeons and clinicians.

Chrysophanol Attenuates Manifestations of Immune Bowel Diseases by Regulation of Colorectal Cells and T Cells Activation In Vivo.

Inflammatory bowel disease (IBD) is an immune disorder that develops due to chronic inflammation in several cells. It is known that colorectal and T cells are mainly involved in the pathogenesis of IBD. Chrysophanol is an anthraquinone family member that possesses several bioactivities, including anti-diabetic, anti-tumor, and inhibitory effects on T cell activation. However, it is unknown whether chrysophanol suppresses the activity of colorectal cells. In this study, we found that chrysophanol did not induce cytotoxicity in HT-29 colorectal cells. Pre-treatment with chrysophanol inhibited the mRNA levels of pro-inflammatory cytokines in tumor necrosis factor-α (TNF-α)-stimulated HT-29 cells. Western blot analysis revealed that pre-treatment with chrysophanol mitigates p65 translocation and the mitogen-activated protein kinase (MAPK) pathway in activated HT-29 cells. Results from the in vivo experiment confirmed that oral administration of chrysophanol protects mice from dextran sulfate sodium (DSS)-induced IBD. Chrysophanol administration attenuates the expression of pro-inflammatory cytokines in colon tissues of the DSS-induced IBD model. In addition, we found that oral administration of chrysophanol systemically decreased the expression of effector cytokines from mesenteric lymph nodes. Therefore, these data suggest that chrysophanol has a potent modulatory effect on colorectal cells as well as exhibiting a beneficial potential for curing IBD in vivo.

Deletion of Irf4 in T Cells Suppressed Autoimmune Uveitis and Dysregulated Transcriptional Programs Linked to CD4+ T Cell Differentiation and Metabolism.

Interferon regulatory factor-4 (IRF4) and IRF8 regulate differentiation, growth and functions of lymphoid and myeloid cells. Targeted deletion of irf8 in T cells (CD4-IRF8KO) has been shown to exacerbate colitis and experimental autoimmune uveitis (EAU), a mouse model of human uveitis. We therefore generated mice lacking irf4 in T cells (CD4-IRF4KO) and investigated whether expression of IRF4 by T cells is also required for regulating T cells that suppress autoimmune diseases. Surprisingly, we found that CD4-IRF4KO mice are resistant to EAU. Suppression of EAU derived in part from inhibiting pathogenic responses of Th17 cells while inducing expansion of regulatory lymphocytes that secrete IL-10 and/or IL-35 in the eye and peripheral lymphoid tissues. Furthermore, CD4-IRF4KO T cells exhibit alterations in cell metabolism and are defective in the expression of two Ikaros zinc-finger (IKZF) transcription factors (Ikaros, Aiolos) that are required for lymphocyte differentiation, metabolism and cell-fate decisions. Thus, synergistic effects of IRF4 and IkZFs might induce metabolic reprogramming of differentiating lymphocytes and thereby dynamically regulate relative abundance of T and B lymphocyte subsets that mediate immunopathogenic mechanisms during uveitis. Moreover, the diametrically opposite effects of IRF4 and IRF8 during EAU suggests that intrinsic function of IRF4 in T cells might be activating proinflammatory responses while IRF8 promotes expansion of immune-suppressive mechanisms.