E3 Ubiquitin Ligase Uhrf2 Knockout Reveals a Critical Role in Social Behavior and Synaptic Plasticity in the Hippocampus.

The hippocampal formation, particularly the CA2 subregion, is critical for social memory formation and memory processing, relying on synaptic plasticity-a fundamental mechanism by which synapses strengthen. Given the role of the ubiquitin-proteasome system (UPS) in various nervous system processes, including learning and memory, we were particularly interested in exploring the involvement of RING-type ubiquitin E3 ligases, such as UHRF2 (NIRF), in social behavior and synaptic plasticity. Our results revealed altered social behavior in mice with systemic Uhrf2 knockout, including changes in nest building, tube dominance, and the three-chamber social novelty test. In Uhrf2 knockout mice, the entorhinal cortex-CA2 circuit showed significant reductions in synaptic plasticity during paired-pulse facilitation and long-term potentiation, while the inability to evoke synaptic plasticity in the Schaffer-collateral CA2 synapses remained unaffected. These changes in synaptic plasticity correlated with significant changes in gene expression including genes related to vesicle trafficking and transcriptional regulation. The effects of Uhrf2 knockout on synaptic plasticity and the observed gene expression changes highlight UHRF2 as a regulator of learning and memory processes at both the cellular and systemic levels. Targeting E3 ubiquitin ligases, such as UHRF2, may hold therapeutic potential for memory-related disorders, warranting further investigation.

Adjunctive azithromycin prophylaxis protects women from uterine cesarean scar defect: A randomized controlled trial.

INTRODUCTION: Cesarean scar defect (CSD) is a long-term outcome of cesarean section (CS) and associated with numerous gynecological and obstetric problems. Previous studies indicate that infection may be a risk factor for CSD. Adjunctive azithromycin was shown to reduce the risk of postoperative infection in patients undergoing non-elective primary cesarean delivery in labor or after the rupture of membranes compared with standard antibiotic prophylaxis. This study investigated the protective effect of adjunctive azithromycin in combination with single-dose cephalosporin against CSD in women undergoing non-elective cesarean delivery. MATERIAL AND METHODS: A randomized, double-blind, controlled clinical trial was conducted in a University hospital in Shanghai, China. A total of 242 women who underwent their first non-elective CS were randomly assigned to receive 1500 mg cefuroxime sodium plus 500 mg intravenous azithromycin (n = 121; experimental group) or 1500 mg cefuroxime sodium plus a placebo (n = 121; placebo group). The primary outcome was CSD prevalence, as determined by transvaginal ultrasound and saline infusion sonohysterography within 6 months of delivery. Secondary outcomes were changes in infectious indicators (eg hypersensitive C-reactive protein and procalcitonin), postoperative morbidity, and use of postoperative antibiotics. We also examined the operative procedure, pathogenic microorganism cultures, and fetal outcomes. Outcomes were compared between groups with the chi-squared test, Fisher's exact test, or Student's t test. RESULTS: Between May 2018 and May 2021, 121 women were randomized to each arm. Because the sonographic follow up was disrupted by the coronavirus disease 2019 pandemic and strict management policies, we merged the follow-up time points (6 weeks and 6 months) into a single time period (6 weeks to 6 months); 104 and 108 women in the experimental and placebo groups, respectively, completed the first sonographic follow up. CSD was diagnosed by sonography in 34/104 (32.7%) and 50/108 (46.3%) patients in the experimental and placebo groups, respectively (relative risk 0.71, 95% confidence interval 0.50-0.99; p = 0.043). Characteristics of CSD and short-term infection outcomes did not differ between groups. CONCLUSIONS: A single dose of intravenous 500 mg azithromycin adjunctive to single-dose cefuroxime prophylaxis significantly reduced the incidence of CSD in women undergoing non-elective CS.

Comparative analysis of the fecal microbiome and metabolomics of healthy versus captive South China tigers with mild diarrhea.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is common among the captive South China tigers in zoos. 16S rRNA gene sequencing was performed to demonstrate the compositions and structures of the gastrointestinal microbiota of this species with IBS-D. Their healthy (F1) and mushy (F2) feces were allocated into two groups. A total of 21 and 31 fecal bacterial communities of major phyla and genera were detected, respectively. The F1 and F2 groups had five common microbiotas at the phylum level (Firmicutes, Proteobacteria, Fusobacteria, Actinobacteria, and Bacteroidetes). Among the five phyla, the abundance of Bacteroidetes in the F2 group was significantly lower than that in the F1 group. The diversity level of fecal microbiota within the mild-diarrhea stool was also significantly lower than that of the healthy counterpart. Thirty-two metabolites were correlated to four genus-level bacteria (Bacteroides, Pseudoclavibacter, Streptococcus, and Ruminococcaceae-UCG-005). Due to its normal role in protein degradation and metabolism, we hypothesized that the lower abundance of Bacteroides within the F2 group could be associated with the IBS-D symptoms. Therefore, this work implied that ameliorating the daily diet with a supplement of probiotics, such as Bacteroides, could improve the gut health of this species.

Flurochloridone induced abnormal spermatogenesis by damaging testicular Sertoli cells in mice.

BACKGROUND: Flurochloridone (FLC), a selective herbicide used on a global scale, has been reported to have male reproductive toxicity whose evidence is limited, but its mechanism remains unclear. The present study was conducted to systematically explore the male reproductive toxicity of FLC, including sperm quality, spermatogenesis, toxicity targets, and potential mechanisms. METHODS: Male C57BL/6 mice aged 6-7 weeks received gavage administration of FLC (365/730 mg/kg/day) for 28 consecutive days. Then, the tissue and sperm of mice were collected for analysis. We measured the gonadosomatic index and analyzed sperm concentration, motility, malformation rate, and mitochondrial membrane potential (MMP). Spermatocyte immunofluorescence staining was performed to analyze meiosis. We also performed pathological staining on the testis and epididymis tissue and TUNEL staining, immunohistochemical analysis, and ultrastructural observation on the testicular tissue. RESULTS: Results showed that FLC caused testicular weight reduction, dysfunction, and architectural damage in mice, but no significant adverse effect was found in the epididymis. The exposure interfered with spermatogonial proliferation and meiosis, affecting sperm concentration, motility, kinematic parameters, morphology, and MMP, decreasing sperm quality. Furthermore, mitochondrial damage and apoptosis of testicular Sertoli cells were observed in mice treated with FLC. CONCLUSION: We found that FLC has significant adverse effects on spermatogonial proliferation and meiosis. Meanwhile, apoptosis and mitochondrial damage may be the potential mechanism of Sertoli cell damage. Our study demonstrated that FLC could induce testicular Sertoli cell damage, leading to abnormal spermatogenesis, which decreased sperm quality. The data provided references for the toxicity risk and research methods of FLC application in the environment.

Comparison of fecal microbiota composition of blue sheep fed Lolium perenne versus Sorghum sudanense.

Lolium perenne L. and Sorghum sudanense (Piper) Stapf. are 2 common forages fed to blue sheep (Pseudois nayaur Hodgson, 1833) in captivity. However, the effect of these 2 forages on the gastrointestinal microbiota is largely unknown. We analyzed the diversity of the microbiota in the feces of captive blue sheep fed with L. perenne (group F1) and S. sudanense (group F2) by 16S rRNA sequencing. A total of 20 major phyla and 29 genera fecal bacterial communities were detected in the 2 groups. The F1 and F2 groups shared common microbiota at the phylum level, which mainly consisted of Firmicutes and Bacteroidetes. Ruminococcaceae_UCG-005, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-013, and Ruminococcaceae_UCG-010 were the top 4 dominant taxa at the genus level. The percentage of Ruminococcaceae_UCG-010 was significantly higher in the F2 group (∼2.75-fold) than in F1 group. The diversity and abundance of the microbial community in F2 was higher than that in F1. Although both of L. perenne and S. sudanense affect the metabolism of the gastrointestinal microbiota of blue sheep, the S. sudanense improves more aspects of metabolism and biogenesis. In summary, our results demonstrated that L. perenne and S. sudanense affect blue sheep gastrointestinal microbiota in different ways. But S. sudanense efficiently improved the gastrointestinal microbiota of blue sheep.

A novel posttranslational modification of histone, H3 S-sulfhydration, is down-regulated in asthenozoospermic sperm.

Oxidative stress is one of the major causes leading to male infertility including asthenozoospermia. Hydrogen sulfide (H2S) has been widely recognized to be a potent antioxidant whose role is partially implemented by protein S-sulfhydration. However, protein S-sulfhydration has not been reported in germ cells. Therefore, we investigated whether asthenozoospermia could be associated with sperm protein S-sulfhydration. S-sulfhydrated proteins in human sperm were enriched via biotin-switch assay and analyzed using LC-MS/MS spectrometry. Two hundred forty-four S-sulfhydrated proteins were identified. Importantly, we validated that sperm histones H3.1 and H3.3 were the S-sulfhydrated proteins. Their S-sulfhydrated amino acid residue was Cysteine111. Abundances of S-sulfhydrated H3 (sH3) and S-sulfhydrated H3.3 (sH3.3) were significantly down-regulated in asthenozoospermic sperm, compared with the fertile controls, and were significantly correlated with progressive motility. Retinoic acid (RA) up-regulated level of sH3.3 in primary round spermatids and the C18-4 cells (a mouse spermatogonial stem cell line). Overexpression of the mutant H3.3 (Cysteine111 was replaced with serine) affected expression of 759 genes and raised growth rate of C18-4 cells. For the first time, S-sulfhydration H3 and H3.3 were demonstrated in the present study. Our results highlight that aberrant S-sulfhydration of H3 is a new pathophysiological basis in male infertility.

Chronic exposure to diesel exhaust particulate matter impairs meiotic progression during spermatogenesis in a mouse model.

Exposure to ambient PM2.5 may correlate with the decline of semen quality, and the underlying biological mechanism has not been fully understood. In the present study, mice were intratracheally instilled with diesel exhaust PM2.5 (DEP), and its effects on the spermatogenic process as well as the alterations of testicular gene expression profile were assessed. Our results showed that chronic exposure to DEP impaired the fertility of male mice without influencing their libido. Compared with Vehicle-exposed group, the sperm count and motility from DEP-exposed mice were significantly decreased. In addition, immunohistological staining of γH2AX and DMC1, biomarkers for meiotic double strand breaks (DSBs), demonstrated that chronic exposure to DEP comprised the repair of meiotic DSBs, thus disrupting the spermatogenesis. Deep RNA sequencing test showed altered expressions of testicular genes including the GnRH signaling pathway. In summary, our research demonstrated that chronic exposure to DEP may disrupt spermatogenesis through targeting the meiotic recombination, providing a new perspective for the research on the male reproductive system damage caused by air pollution.

The cell line ontology-based representation, integration and analysis of cell lines used in China.

BACKGROUND: The Chinese National Infrastructure of Cell Line stores and distributes cell lines for biomedical research in China. This study aims to represent and integrate the information of NICR cell lines into the community-based Cell Line Ontology (CLO). RESULTS: We have aligned, represented, and added all identified 2704 cell line cells in NICR to CLO. We also proposed new ontology design patterns to represent the usage of cell line cells as disease models by inducing tumor formation in model organisms, and the relations between cell line cells and their expressed or overexpressed genes or proteins. The resulting CLO-NICR ontology also includes the Chinese representation of the NICR cell line information. CLO-NICR was merged into the general CLO. To serve the cell research community in China, the Chinese version of CLO-NICR was also generated and deposited in the OntoChina ontology repository. The usage of CLO-NICR was demonstrated by DL query and knowledge extraction. CONCLUSIONS: In summary, all identified cell lines from NICR are represented by the semantics framework of CLO and incorporated into CLO as a most recent update. We also generated a CLO-NICR and its Chinese view (CLO-NICR-Cv). The development of CLO-NICR and CLO-NIC-Cv allows the integration of the cell lines from NICR into the community-based CLO ontology and provides an integrative platform to support different applications of CLO in China.

The prevalence and risk predictors of cesarean scar defect at 6 weeks postpartum in Shanghai, China: A prospective cohort study.

INTRODUCTION: The aim of this study was to explore the prevalence and predictors of cesarean scar defect (CSD) at 6 weeks postpartum in Shanghai, China. MATERIAL AND METHODS: Women scheduled to receive a cesarean section (CS) were recruited from a university hospital. Surgery-related factors, pregnancy complications, routine examinations, perioperative medications, and physical signs were collected and transvaginal ultrasonography was performed to assess the presence of a CSD at 6 weeks postpartum. Multivariate logistic regression was applied to identify the predictors for CSD. RESULTS: A CSD was detected in 223 of 514 women (43.4%, 95% CI 39.1%-47.7%) by transvaginal ultrasonography. Of women with normal temperature (T < 37.5°C, CSD prevalence 33.9%, 95% CI 28.4%-39.5%), women with postpartum fever (T ≥ 38°C, CSD 44.1%, 95% CI 31.0%-57.1%), and women who were subfebrile in the postpartum (37.5 ≤ T ≤ 38.0°C, CSD 58.3%, 95% CI 50.9%-65.7%), the latter two had significantly increased risk for CSD (adjusted odds ratio [aOR] 2.7, 95% CI 1.3-5.2 and aOR 3.3, 95% CI 2.1-5.3, respectively). In comparison to single-dose antibiotic administration (CSD 49.0%, 95% CI 43.8%-54.3%), multi-dose antibiotic administration (CSD 31.1%, 95% CI 23.8%-38.3%) had a protective effect (aOR 0.4, 95% CI 0.3-0.7). Postpartum fever, intrapartum infection, emergency CS, and cervical dilation ≥ 3 cm were found to be the main predictors of multi-dose antibiotics management. Low platelet count postpartum (defined as ≤ 150 × 109 /L) and high fibrinogen pre-CS (defined as ≥ 4.5 g/L) increased CSD risk (aOR 2.0, 95% CI 1.1-3.6 and 1.7, 95% CI 1.1-2.5, respectively). CONCLUSIONS: The prevalence of CSD in the Chinese population is high enough to be a concern. Perioperative infection and hypercoagulability should be considered CSD predictors, and multi-dose antibiotics have a protective effect.

Left-Right Asymmetry of Tubal Pregnancy: A 12-Year Retrospective Hospital-Based Study.

STUDY OBJECTIVE: To investigate whether there are left-right asymmetries, factors affecting lateral dominance, and clinical feature differences in the left and right sides of tubal pregnancy (TP). DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University. PATIENTS: Patients (n = 6186) with TP treated surgically. INTERVENTIONS: We used data from the digital medical records system of the hospital. Women diagnosed with ectopic pregnancy(EP) between January 2005 and December 2016 in the inpatient department of gynecology were included. All data from the medical files were obtained retrospectively, including demographic characteristics; reproductive, gynecologic, and surgical history; clinical features; and treatment. Patients who were previously treated by salpingectomy or nonsurgical management and those with unknown-site EP or non-TPs were excluded. MEASUREMENTS AND MAIN RESULTS: The overall frequency of right-sided TP was 54.48% (3370/6186), which is significantly higher than 50% (p < .001, binominal test). The proportion of right-sided TPs decreased with age (p for trend = .007) and from the proximal (interstitial) end to the distal (fimbrial) end of the tube (p for trend = .017). Of the TP patients with a corpus luteum, we found the corpus luteum was more frequently located in the right ovary (p < .001) and in the contralateral ovary to the TP side in 41.38% of cases. However, tubal rupture was more frequent in left TP than the in right TP (p = .005). CONCLUSION: The left-right asymmetries of TP include right-side dominance and the clinical feature differences between the 2sides of TP.

Ontology: Footstone for Strong Artificial Intelligence.

In the past ten years, the application of artificial intelligence (AI) in biomedicine has increased rapidly, which roots in the rapid growth of biomedicine data, the improvement of computing performance, and the development of deep learning methods. At present, there are great difficulties in front of AI for solving complex and comprehensive medical problems. Ontology can play an important role in how to make machines have stronger intelligence and has wider applications in the medical field. By using ontologies, (meta) data can be standardized so that data quality is improved and more data analysis methods can be introduced, data integration can be supported by the semantics relationships which are specified in ontologies, and effective logic expression in nature language can be better understood by machine. This can be a pathway to stronger AI. Under this circumstance, the Chinese Conference on Biomedical Ontology and Terminology was held in Beijing in autumn 2019, with the theme "Making Machine Understand Data". The success of this conference further improves the development of ontology in the field of biomedical information in China, and will promote the integration of Chinese ontology research and application with the international standards and the findability, accessibility, interoperability, and reusability(FAIR) Data Principle.

Ontology: Footstone for Strong Artificial Intelligence.

In the past ten years, the application of artificial intelligence (AI) in biomedicine has increased rapidly, which roots in the rapid growth of biomedicine data, the improvement of computing performance, and the development of deep learning methods. At present, there are great difficulties in front of AI for solving complex and comprehensive medical problems. Ontology can play an important role in how to make machines have stronger intelligence and has wider applications in the medical field. By using ontologies, (meta) data can be standardized so that data quality is improved and more data analysis methods can be introduced, data integration can be supported by the semantics relationships which are specified in ontologies, and effective logic expression in nature language can be better understood by machine. This can be a pathway to stronger AI. Under this circumstance, the Chinese Conference on Biomedical Ontology and Terminology was held in Beijing in autumn 2019, with the theme "Making Machine Understand Data". The success of this conference further improves the development of ontology in the field of biomedical information in China, and will promote the integration of Chinese ontology research and application with the international standards and the findability, accessibility, interoperability, and reusability(FAIR) Data Principle.

Lgr4-mediated Wnt/ß-catenin signaling in peritubular myoid cells is essential for spermatogenesis.

Peritubular myoid cells (PMCs) are myofibroblast-like cells that surround the seminiferous tubules and play essential roles in male fertility. How these cells modulate spermatogenesis and the signaling pathways that are involved are largely unknown. Here we report that Lgr4 is selectively expressed in mouse PMCs in the testes, and loss of Lgr4 leads to germ cells arresting at meiosis I and then undergoing apoptosis. In PMCs of Lgr4 mutant mice, the expression of androgen receptor, alpha-smooth muscle actin and extracellular matrix proteins was dramatically reduced. Malfunctioning PMCs further affected Sertoli cell nuclear localization and functional protein expression in Lgr4(-/-) mice. In addition, Wnt/ß-catenin signaling was activated in wild-type PMCs but attenuated in those of Lgr4(-/-) mice. When Wnt/ß-catenin signaling was reactivated by crossing with Apc(min/+) mice or by Gsk3ß inhibitor treatment, the Lgr4 deficiency phenotype in testis was partially rescued. Together, these data demonstrate that Lgr4 signaling through Wnt/ß-catenin regulates PMCs and is essential for spermatogenesis.

The dual regulatory role of miR-204 in cancer.

MicroRNAs (miRNAs) are a group of endogenous, small (about 22 nucleotides) non-coding RNAs which negatively regulate gene expressions. As one of them, miR-204 originates from the sixth intron of the transient receptor potential melastatin 3 (TRPM3) gene. Therefore, expression of miR-204 is under the control of the TRPM3 promoter and regulated by genetic and epigenetic mechanisms. miR-204 has been found to play the important roles in development of eyes and adipogenesis. Its pathological functions have been observed in a few diseases including pulmonary arterial hypertension, diabetes, and various types of cancers. It is believed that miR-204 acts as a tumor-suppressor via promoting apoptosis, conferring the resistance of cancer cells to chemotherapy, and suppressing the self-renewal of cancer stem cells (CSCs) and the epithelial to mesenchymal transition (EMT). Expression of miR-204 is repressed by its targets XRN1 and TRKB in prostate cancer and endometrial carcinoma, respectively; therefore, they establish an oncogenic feedback loops that play an important role promoting development of cancer. In this review, we summarize our current knowledge regarding miR-204, including its expression, regulation and biological functions, especially focusing our discussion on its role in tumor development and tumor progression.

A Facile Approach to Optically Active Hydroquinoline-2-carboxylates by a One-Pot Asymmetric Michael/Transamination/Cyclization Process.

An efficient one-pot synthesis of optically active hydroquinoline-2-carboxylates from 1,3-cyclohexanediones, ß,γ-unsaturated α-keto ester, and benzylamine in the presence of a chiral base catalyst and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with good diastereoselectivity and high enantioselectivity is described. The reaction proceeds by a sequential asymmetric Michael/transamination/cyclization process.

Sustained activation of mTORC1 in macrophages increases AMPKα-dependent autophagy to maintain cellular homeostasis.

BACKGROUND: The mechanistic target of rapamycin complex 1 (mTORC1) is a well-conserved serine/threonine protein kinase that controls autophagy as well as many other processes such as protein synthesis, cell growth, and metabolism. The activity of mTORC1 is stringently and negatively controlled by the tuberous sclerosis proteins 1 and 2 complex (TSC1/2). RESULTS: In contrast to the previous studies using Tsc1 knockout mouse embryonic fibroblasts (MEF) cells, we demonstrated evidence that TSC1 deficient macrophages exhibited enhanced basal and mycobacterial infection-induced autophagy via AMPKα-dependent phosphorylation of ULK1 (Ser555). These effects were concomitant with constitutive activation of mTORC1 and can be reversed by addition of amino acids or rapamycin, and by the knockdown of the regulatory-associated protein of mTOR, Raptor. In addition, increased autophagy in TSC1 deficient macrophages resulted in suppression of inflammation during mycobacterial infection, which was reversed upon amino acid treatment of the TSC1 deficient macrophages. We further demonstrated that TSC1 conditional knockout mice infected with Mycobacterium tuberculosis, the causative agent of tuberculosis, resulted in less bacterial burden and a comparable level of inflammation when compared to wild type mice. CONCLUSIONS: Our data revealed that sustained activation of mTORC1 due to defects in TSC1 promotes AMPKα-dependent autophagic flux to maintain cellular homeostasis.

Progress in asymmetric biomimetic transamination of carbonyl compounds.

Transamination of α-keto acids with transaminases and pyridoxamine phosphate is an important process to form optically active α-amino acids in biological systems. Various biomimetic transamination systems have been developed for carbonyl compounds including α-keto acid derivatives, fluoroalkyl ketones, and unactivated ketones with chiral vitamin B6 analogues, artificial transaminase mimics, chiral nitrogen sources, and chiral catalysts. This review provides a brief summary of this area.

Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses.

Cerebellar dysfunction causes ataxia characterized by loss of balance and coordination. Until now, the molecular and neuronal mechanisms of several types of inherited cerebellar ataxia have not been completely clarified. Here, we report that leucine-rich G protein-coupled receptor 4 (Lgr4/Gpr48) is highly expressed in Purkinje cells (PCs) in the cerebellum. Deficiency of Lgr4 leads to an ataxia-like phenotype in mice. Histologically, no obvious morphological changes were observed in the cerebellum of Lgr4 mutant mice. However, the number of PCs was slightly but significantly reduced in Lgr4(-/-) mice. In addition, in vitro electrophysiological analysis showed an impaired long term depression (LTD) at parallel fiber-PC (PF-PC) synapses in Lgr4(-/-) mice. Consistently, immunostaining experiments showed that the level of phosphorylated cAMP-responsive element-binding protein (Creb) was significantly decreased in Lgr4(-/-) PCs. Furthermore, treatment with forskolin, an adenylyl cyclase agonist, rescued phospho-Creb in PCs and reversed the impairment in PF-PC LTD in Lgr4(-/-) cerebellar slices, indicating that Lgr4 is an upstream regulator of Creb signaling, which is underlying PF-PC LTD. Together, our findings demonstrate for first time an important role for Lgr4 in motor coordination and cerebellar synaptic plasticity and provide a potential therapeutic target for certain types of inherited cerebellar ataxia.

Enantioselective 6-endo bromoaminocyclization of 2,4-dienyl N-tosylcarbamates catalyzed by a chiral phosphine oxide-Sc(OTf)3 complex. A dramatic additive effect.

An effective enantioselective 6-endo bromoaminocyclization of 2,4-dienyl N-tosylcarbamates catalyzed by a chiral phosphine oxide-Sc(OTf)3 complex is described. A wide variety of optically active 5-bromo-1,3-oxazinan-2-ones containing various functional groups can be obtained in 61-91% yields and 92-99% ees. An additive, such as NaCl, has been found to be crucial for the reaction process.

Critical role of the tumor suppressor tuberous sclerosis complex 1 in dendritic cell activation of CD4 T cells by promoting MHC class II expression via IRF4 and CIITA.

Dendritic cell (DC) maturation is characterized by upregulation of cell-surface MHC class II (MHC-II) and costimulatory molecules, and production of a variety of cytokines that can shape both innate and adaptive immunity. Paradoxically, transcription of the MHC-II genes, as well as its activator, CIITA, is rapidly silenced during DC maturation. The mechanisms that control CIITA/MHC-II expression and silencing have not been fully understood. We report in this article that the tumor suppressor tuberous sclerosis complex 1 (TSC1) is a critical regulator of DC function for both innate and adaptive immunity. Its deficiency in DCs results in increased mammalian target of rapamycin (mTOR) complex 1 but decreased mTORC2 signaling, altered cytokine production, impaired CIITA/MHC-II expression, and defective Ag presentation to CD4 T cells after TLR4 stimulation. We demonstrate further that IFN regulatory factor 4 can directly bind to CIITA promoters, and decreased IFN regulatory factor 4 expression is partially responsible for decreased CIITA/MHC-II expression in TSC1-deficient DCs. Moreover, we identify that CIITA/MHC-II silencing during DC maturation requires mTOR complex 1 activity. Together, our data reveal unexpected roles of TSC1/mTOR that control multifaceted functions of DCs.