7-Ketocholesterol plays a key role in cholesterol-induced hepatitis via macrophage and neutrophil infiltration.

This study sought to explore the role of 7-ketocholesterol (7-KC) in liver damage caused by high cholesterol intake and its potential pathological mechanism in mice. Our in vivo findings indicated that mice fed a high-cholesterol diet had elevated serum levels of 7-KC, accompanied by liver injury and inflammation, similar to human nonalcoholic steatohepatitis. Furthermore, the high-cholesterol diet induced neutrophil infiltration, which played a critical role in liver damage through myeloperoxidase (MPO) activity. Upon stimulation with 7-KC, macrophages exhibited increased expression of C-X-C motif chemokine ligand 1 (CXCL1) and CXCL2, as well as ATP-binding cassette transporter A1 (ABCA1) and ABCG1. Hepatocytes, on the other hand, exhibited increased expression of CXCL2 and ABCG1. The infiltration of neutrophils in the liver was primarily caused by CXCL1 and CXCL2, resulting in hepatocyte cell death due to elevated MPO activity. Our data also revealed that the activation of macrophages by 7-KC via ABCA1 or ABCG1 was not associated with lipid accumulation. Collectively, these findings suggest that high cholesterol-induced hepatitis in mice involves, at least partially, the recruitment of neutrophils to the liver by 7-KC-activated macrophages. This is mediated by increased expression of CXCL1 and CXCL2 through ABCA1 or ABCG1, which act as 7-KC efflux transporters. Additionally, hepatocytes contribute to this process by increased expression of CXCL2 through ABCG1. Therefore, our findings suggest that 7-KC may play a role in high cholesterol-induced hepatitis in mice by activating macrophages and hepatocytes, ultimately leading to neutrophil infiltration.

Estrogen Decreases Cytoskeletal Organization by Forming an ERα/SHP2/c-Src Complex in Osteoclasts to Protect against Ovariectomy-Induced Bone Loss in Mice.

Loss of ovarian function is closely related to estrogen (E2) deficiency, which is responsible for increased osteoclast (OC) differentiation and activity. We aimed to investigate the action mechanism of E2 to decrease bone resorption in OCs to protect from ovariectomy (OVX)-induced bone loss in mice. In vivo, tartrate-resistant acid phosphatase (TRAP) staining in femur and serum carboxy-terminal collagen crosslinks-1 (CTX-1) were analyzed upon E2 injection after OVX in mice. In vitro, OCs were analyzed by TRAP staining, actin ring formation, carboxymethylation, determination of reactive oxygen species (ROS) level, and immunoprecipitation coupled with Western blot. In vivo and in vitro, E2 decreased OC size more dramatically than OC number and Methyl-piperidino-pyrazole hydrate dihydrochloride (MPPD), an estrogen receptor alpha (ERα) antagonist, augmented the OC size. ERα was found in plasma membranes and E2/ERα signaling affected receptor activator of nuclear factor κB ligand (RANKL)-induced actin ring formation by rapidly decreasing a proto-oncogene tyrosine-protein kinase, cellular sarcoma (c-Src) (Y416) phosphorylation in OCs. E2 exposure decreased physical interactions between NADPH oxidase 1 (NOX1) and the oxidized form of c-Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), leading to higher levels of reduced SHP2. ERα formed a complex with the reduced form of SHP2 and c-Src to decrease c-Src activation upon E2 exposure, which blocked a signal for actin ring formation by decreased Vav guanine nucleotide exchange factor 3 (Vav3) (p-Y) and Ras-related C3 botulinum toxin substrate 1 (Rac1) (GTP) activation in OCs. E2/ERα signals consistently inhibited bone resorption in vitro. In conclusion, our study suggests that E2-binding to ERα forms a complex with SHP2/c-Src to attenuate c-Src activation that was induced upon RANKL stimulation in a non-genomic manner, resulting in an impaired actin ring formation and reducing bone resorption.

Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase-1.

Loss of ovarian function results in increased fat mass, leading to the accumulation of adipose tissue macrophages that participate in chronic inflammation. We hypothesized that ovariectomy (OVX)-induced increases in body weight and fat mass are associated with decreased adipose tissue (AT) browning due to estrogen (E2 ) deficiency. In mice, OVX decreased AT browning along with increased body weight, fat mass, and size of lipid droplets 12 weeks after surgery. Exogenous E2 recovered the OVX-induced changes. AT browning was enhanced by M2 macrophages induced by exogenous E2. E2 -induced M2 polarization occurred due to the increased expression of heme oxygenase-1 (HO-1) in macrophages, leading to decreased reactive oxygen species levels. Collectively, we demonstrated that E2 enhances AT browning via M2 polarization mediated by HO-1.

Tonicity-responsive enhancer-binding protein promotes stemness of liver cancer and cisplatin resistance.

BACKGROUND: High recurrence and chemoresistance drive the high mortality in hepatocellular carcinoma (HCC). Although cancer stem cells are considered to be the source of recurrent and chemoresistant tumors, they remain poorly defined in HCC. Tonicity-responsive enhancer binding protein (TonEBP) is elevated in almost all HCC tumors and associated with recurrence and death. We aimed to identify function of TonEBP in stemness and chemoresistance of liver cancer. METHODS: Tumors obtained from 280 HCC patients were analyzed by immunohistochemical analyses. Stemness and chemoresistance of liver CSCs (LCSCs) were investigated using cell culture. Tumor-initiating activity was measured by implanting LCSCs into BALB/c nude mice. FINDINGS: Expression of TonEBP is higher in LCSCs in HCC cell lines and correlated with markers of LCSCs whose expression is significantly associated with poor prognosis of HCC patients. TonEBP mediates ATM-mediated activation of NF-κB, which stimulates the promoter of a key stem cell transcription factor SOX2. As expected, TonEBP is required for the tumorigenesis and self-renewal of LSCSs. Cisplatin induces the recruitment of the ERCC1/XPF dimer to the chromatin in a TonEBP-dependent manner leading to DNA repair and cisplatin resistance. The cisplatin-induced inflammation in LSCSs is also dependent on the TonEBP-ERCC1/XPF complex, and leads to enhanced stemness via the ATM-NF-κB-SOX2 pathway. In HCC patients, tumor expression of ERCC1/XPF predicts recurrence and death in a TonEBP-dependent manner. INTERPRETATION: TonEBP promotes stemness and cisplatin resistance of HCC via ATM-NF-κB. TonEBP is a key regulator of LCSCs and a promising therapeutic target for HCC and its recurrence.

Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), is one of the specific type of low-grade B-cell lymphoma not infrequently found worldwide. It typically involves mucosal sites such as stomach and conjunctiva; however, primary hepatic MALT lymphoma has been extremely rarely reported. We describe a case of hepatic MALT lymphoma in a 70-year-old male patient who underwent left hepatectomy due to the incidentally detected liver masses at a medical checkup. The resected specimen revealed multinodular masses consisting of small-to-intermediate-sized lymphoid cells with serpentine pattern and focal lymphoepithelial lesions. The tumor cells were diffusely positive for CD20 and Bcl-2 but negative for CD3, CD10, CD5, CD23, CD43, and cyclinD1. The Ki-67 labeling index was 10% and immunoglobulin heavy chain gene rearrangement study confirmed monoclonal proliferation. In this paper, we discuss several unique clinicopathologic characteristics which will be helpful to the differential diagnosis of hepatic MALT lymphoma.

Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer.

BACKGROUND: Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC). METHODS: We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed. RESULTS: PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05). CONCLUSIONS: The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.

Atherogenic diet-induced bone loss is primarily due to increased osteoclastogenesis in mice.

Atherogenic diet (AD) decreased bone density and increased serum cholesterol level in male mice, implying that cholesterol participates in bone loss. The aim of the present study was to identify the cells responsible for bone loss and evaluate the involved mechanism. AD resulted in increased number and surface of osteoclasts (OCs) with in vivo tartrate-resistant acid phosphatase (TRAP) staining, suggesting a critical role of OCs in cholesterol-induced bone loss. In vitro, cholesterol loading by oxidized low-density lipoprotein (oxLDL) increased the size and number of OCs as well as bone resorption activity, suggesting that cholesterol loading affects the number and activity of OCs. In contrast, cholesterol depletion by simvastatin decreased osteoclastogenesis and bone resorption. oxLDL stimulated osteoblasts (OBs) to increase expression of receptor activator of nuclear factor kappa-Β ligand (RANKL), resulting in increased OC formation when OBs were co-cultured with bone marrow derived macrophages. oxLDL increased expression of CD36 and liver X receptors (LXRα) in OCs as well as low density lipoprotein receptor (LDLR) and LXRα in OBs. These results suggest that CD36 and LXRα mediate the effect of oxLDL in OCs, whereas LDLR and LXRα mediate the effect of oxLDL in OBs. These findings demonstrate cholesterol-induced bone loss with increasing number and activity of OCs in mice, suggesting another harmful effect of cholesterol, a major cause of atherosclerosis.

MCP-1 deficiency enhances browning of adipose tissue via increased M2 polarization.

Obesity is strongly associated with chronic inflammation for which adipose tissue macrophages play a critical role. The objective of this study is to identify monocyte chemoattractant protein-1 (MCP-1, CCL2) as a key player governing M1-M2 macrophage polarization and energy balance. We evaluated body weight, fat mass, adipocyte size and energy expenditure as well as core body temperature of Ccl2 knockout mice compared with wild-type mice. Adipose tissues, differentiated adipocyte and bone marrow-derived macrophages were assessed by qPCR, Western blot analysis and histochemistry. MCP-1 deficiency augmented energy expenditure by promoting browning in white adipose tissue and brown adipose tissue activity via increasing the expressions of Ucp1, Prdm16, Tnfrsf9, Ppargc1a, Nrf1 and Th and mitochondrial DNA copy number. MCP-1 abrogation promoted M2 polarization which is characterized by increased expression of Arg1, Chil3, Il10 and Klf4 whereas it decreased M1 polarization by decreased p65 nuclear translocation and attenuated expression of Itgax, Tnf and Nos2, leading to increased browning of adipocytes. Enhanced M2 polarization and attenuated M1 polarization in the absence of MCP-1 are independent. Collectively, our results suggest that the action of MCP-1 in macrophages modulates energy expenditure by impairing browning in adipose tissue.

Tonicity-responsive enhancer-binding protein promotes hepatocellular carcinogenesis, recurrence and metastasis.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse aetiological agents and wide heterogeneity in individual tumours impede effective and personalised treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of proinflammatory genes. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify function of TonEBP in HCC. DESIGN: Tumours with surrounding hepatic tissues were obtained from 296 patients with HCC who received completion resection. TonEBP expression was analysed by quantitative reverse transcription-quantitative real-time PCR (RT-PCR) and immunohfistochemical analyses of tissue microarrays. Mice with TonEBP haplodeficiency, and hepatocyte-specific and myeloid-specific TonEBP deletion were used along with HCC and hepatocyte cell lines. RESULTS: TonEBP expression is higher in tumours than in adjacent non-tumour tissues in 92.6% of patients with HCC regardless of aetiology associated. The TonEBP expression in tumours and adjacent non-tumour tissues predicts recurrence, metastasis and death in multivariate analyses. TonEBP drives the expression of cyclo-oxygenase-2 (COX-2) by stimulating the promoter. In mouse models of HCC, three common sites of TonEBP action in response to diverse aetiological agents leading to tumourigenesis and tumour growth were found: cell injury and inflammation, induction by oxidative stress and stimulation of the COX-2 promoter. CONCLUSIONS: TonEBP is a key component of the common pathway in tumourigenesis and tumour progression of HCC in response to diverse aetiological insults. TonEBP is involved in multiple steps along the pathway, rendering it an attractive therapeutic target as well as a prognostic biomarker.

Ultrasonographic Features of Eccrine Spiradenoma.

The purpose of this series was to evaluate the features of eccrine spiradenoma on ultrasonography (US). We reviewed the clinical data of 8 patients with eccrine spiradenoma who underwent preoperative US at 4 different medical institutions from 2004 to 2016 and analyzed the US features in terms of the tumor location, size, shape, margin, echo texture, echogenicity, posterior acoustic enhancement, calcification, septum, and color Doppler flow. There were 7 female patients and 1 male patient. The mean patient age was 45.6 years (range, 28-60 years). Most of the tumors were located primarily in the subcutaneous fat layer. The mean size of the tumors was 14.3 mm. The masses had a lobular appearance in 7 patients and had a tractlike structure in 3 patients. In 6 patients, the masses had a heterogeneous echo texture. Six cases showed hypoechogenicity with more hypoechoic foci in the masses, and 2 cases showed hypoechogenicity only. Color Doppler flow was evaluated in 7 patients; the blood flow was central and peripheral in 4 patients and only peripheral in 3 patients. All cases showed posterior acoustic enhancement and had well-defined margins. Calcification and septa were not seen in any cases. Eccrine spiradenoma is usually located in the subcutaneous fat layer, has a well-defined margin, a lobulated appearance, occasionally with a tractlike structure, a heterogeneous echo texture, a hypoechoic appearance with internal hypoechoic foci and posterior acoustic enhancement, and shows blood flow in the peripheral portion, with or without blood flow in the central portion.

Lack of NOD2 attenuates ovariectomy-induced bone loss via inhibition of osteoclasts.

Nucleotide-binding oligomerization domain-2 (NOD2) is a pattern recognition receptor of the innate immune system. It interacts with serine-threonine kinases to induce activation of nuclear factor κB (NF-κB), which is important for receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. We tested the idea that NOD2 modulates bone metabolism via an action on osteoclasts (OCs). The absence of NOD2 reduced ovariectomy-induced bone loss in mice, and lowered the area and the activity of OCs, by impairing RANKL signaling. It also reduced the level of reactive oxygen species (ROS), as well as of NF-κB-DNA binding upon RANKL exposure. NOD2 was found to physically interact with nicotinamide adenine dinucleotide phosphate oxidase 1, and this led to increased production of ROS in OCs. Our data suggest that NOD2 contributes to bone loss in estrogen deficiency by elevating ROS levels in OCs.

Concurrent Gastric Adenocarcinoma of Fundic Gland Type and Carcinoma with Lymphoid Stroma: A Rare Case Report.

Both gastric adenocarcinoma of fundic gland type (ADC-FG) and carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma, LELC) are relatively rare. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of LELC. However, the pathogenesis of ADC-FG, as well as the role of EBV in the carcinogenesis of LELC, remain unclear and under debate. The current study presents a case of concurrent ADC-FG and LELC in the stomach in a 69-year-old man. Total gastrectomy was performed, and two separate masses were identified. Upon histological and immunohistochemical examination, the mass located in the lower body was determined to be LELC and the mass in the upper body was diagnosed as ADC-FG. The lesions were characterized by different mucin phenotypes and EBV in situ results. In the lower-body mass, EBV in situ hybridization expression was diffusely strongly positive, but MUC2, MUC5AC, MUC6, and CD10 were all negative. On the other hand, in the upper-body mass, the results were positive for MUC6 but negative for MUC2, MUC5AC, CD10, and EBV by in situ hybridization. The remaining gastric tissue was unremarkable, and perigastric lymph node metastases were absent. Seven months after the gastrectomy, a postoperative computed tomography scan revealed no recurrence or metastasis.

MRI features of calcifying aponeurotic fibroma in the upper arm: a case report and review of the literature.

Calcifying aponeurotic fibroma is a rare soft tissue tumor that occurs in the distal extremities of children and adolescents. We report a case of pathologically proven calcifying aponeurotic fibroma in the left upper arm of a 23-year-old female. Radiographs revealed increased soft tissue density with multiple stippled calcifications in the mid-portion of the patient's left upper arm. Magnetic resonance imaging (MRI) showed a well-defined soft tissue mass with low to intermediate signal intensity on T1-weighted images, heterogeneously low signal intensity on T2-weighted images, and heterogeneous enhancement on fat-suppressed, contrast-enhanced T1-weighted images. Histologically, spindle cell proliferation with scattered calcifications and hyalinization was present. Seven years after surgery, there was no evidence of local recurrence. This is the first report of MRI findings of calcifying aponeurotic fibroma in the upper arm. We also summarize the MRI findings of 16 previously reported cases of calcifying aponeurotic fibroma originating in the upper or lower extremities.

Pure Intrasellar Meningioma Mimicking Pituitary Macroadenoma: Magnetic Resonance Imaging and Review of the Literature.

Intrasellar meningioma originating from the sellar floor is extremely rare and is often indistinguishable from pituitary macroadenoma, both clinically and radiologically. Here, we report a case involving a 68-year-old patient with intrasellar meningioma possibly originating from the sellar floor and present a brief review of all previous cases reported in the English literature.

Cilostazol attenuates ovariectomy-induced bone loss by inhibiting osteoclastogenesis.

BACKGROUND: Cilostazol has been reported to alleviate the metabolic syndrome induced by increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels, which is also associated with osteoclast (OC) differentiation. We hypothesized that bone loss might be attenuated via an action on OC by cilostazol. METHODOLOGY AND PRINCIPAL FINDINGS: To test this idea, we investigated the effect of cilostazol on ovariectomy (OVX)-induced bone loss in mice and on OC differentiation in vitro, using µCT and tartrate-resistant acid phosphatase staining, respectively. Cilostazol prevented from OVX-induced bone loss and decreased oxidative stress in vivo. It also decreased the number and activity of OC in vitro. The effect of cilostazol on reactive oxygen species (ROS) occurred via protein kinase A (PKA) and cAMP-regulated guanine nucleotide exchange factor 1, two major effectors of cAMP. Knockdown of NADPH oxidase using siRNA of p47phox attenuated the inhibitory effect of cilostazol on OC formation, suggesting that decreased OC formation by cilostazol was partly due to impaired ROS generation. Cilostazol enhanced phosphorylation of nuclear factor of activated T cells, cytoplasmic 1 (NFAT2) at PKA phosphorylation sites, preventing its nuclear translocation to result in reduced receptor activator of nuclear factor-κB ligand-induced NFAT2 expression and decreased binding of nuclear factor-κB-DNA, finally leading to reduced levels of two transcription factors required for OC differentiation. CONCLUSIONS/SIGNIFICANCE: Our data highlight the therapeutic potential of cilostazol for attenuating bone loss and oxidative stress caused by loss of ovarian function.

Hemeoxygenase-1 maintains bone mass via attenuating a redox imbalance in osteoclast.

Heme oxygenase-1 (HO-1) has long been considered to be an endogenous antioxidant. However, the role of HO-1 is highly controversial in developing metabolic diseases. We hypothesized that HO-1 plays a role in maintaining bone mass by alleviating a redox imbalance. We investigated its role in bone remodeling. The absence of HO-1 in mice led to decreased bone mass with elevated activity and number of OCs, as well as higher serum levels of reactive oxygen species (ROS). HO-1, which is constitutively expressed at a high level in osteoclast (OC) precursors, was down-regulated during OC differentiation. HO-1 deficiency in bone marrow macrophages (BMM) in vitro resulted in increased numbers and activity of OCs due to enhanced receptor activator of nuclear factor-κB ligand (RANKL) signaling. This was associated with increased activation of nuclear factor-κB and of nuclear factor of activated T-cells, cytoplasmic 1 along with elevated levels of intracellular calcium and ROS. Decreased bone mass in the absence of HO-1 appears to be mainly due to increased osteoclastogenesis and bone resorption resulting from elevated RANKL signaling in OCs. Our data highlight the potential role of HO-1 in maintaining bone mass by negatively regulating OCs.

Case of bronchoesophageal fistula with gastric perforation due to multidrug-resistant tuberculosis.

Gastric perforation and tuberculous bronchoesophageal fistula (TBEF) are very rare complications of extrapulmonary tuberculosis (TB). We present a case of pulmonary TB with TBEF and gastric perforation caused by a multidrug-resistant tuberculosis strain in a non-acquired immune deficiency syndrome male patient. The patient underwent total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy and feeding jejunostomy during intravenous treatment with anti-TB medication, and esophageal reconstruction with colonic interposition and jejunocolostomy were performed successfully after a full course of anti-TB medication. Though recent therapies for TBEF have favored medication, patients with severe stenosis or perforation require surgery and medication with anti-TB drugs based upon adequate culture and drug susceptibility testing.

Extraskeletal osteosarcoma arising from the pleura.

A 37-year-old woman was referred to our institution for further management of a mass lesion located in the thoracic cavity. The mass had grown by more than 10 cm over the course of a year and was initially considered to be a scar from previous pulmonary tuberculosis at another hospital. The patient had complained of left-sided flank pain for a year and experienced dyspnea for one month. Chest radiography and chest computed tomography revealed an irregular-shaped mass in the left mid to lower pleural cavity. The mass was widely excised through left thoracotomy. Pathologic examination of the biopsy specimen revealed a malignant spindle cell tumor, which consisted of components of osteosarcoma, pleomorphic sarcoma, and leiomyosarcoma. The patient underwent adjuvant chemotherapy and has been doing well without any evidence of recurrence for 14 months.

Developmentally regulated GTP-binding protein 2 ameliorates EAE by suppressing the development of TH17 cells.

Developmentally regulated GTP-binding protein 2 (DRG2) represents a novel subclass of GTP-binding proteins. We here report that transgenic overexpression of DRG2 in mice ameliorates experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The protective effect of DRG2 in EAE was mediated by the inhibition of the development of T(H)17 cells. DRG2 enhanced the activity of PPARγ, which led to an inhibition of the nuclear factor kappa B (NF-κB) activity and IL-6 production in antigen presenting cells and an inhibition of the development of T(H)17 cells. Our results demonstrate that DRG2 is an essential modulator of EAE.

TNFRSF14 deficiency protects against ovariectomy-induced adipose tissue inflammation.

To elucidate the role of tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in metabolic disturbance due to loss of ovarian function, ovariectomy (OVX) was performed in TNFRSF 14-knockout mice. OVX increased fat mass and infiltration of highly inflammatory CD11c cells in the adipose tissue (AT), which was analyzed by flow cytometry, and resulted in disturbance of glucose metabolism, whereas TNFRSF14 deficiency attenuated these effects. TNFRSF14 deficiency decreased recruitment of CD11c-expressing cells in AT and reduced the polarization of bone marrow-derived macrophages to M1. Upon engagement of LIGHT, a TNFRSF14 ligand, TNFRSF14 enhanced the expression of CD11c via generation of reactive oxygen species, suggesting a role of TNFRSF14 as a redox modulator. TNFRSF14 participated in OVX-induced AT inflammation via upregulation of CD11c, resulting in metabolic perturbation. TNFRSF14 could be used as a therapeutic target for the treatment of postmenopausal syndrome by reducing AT inflammation.