ARCHIVES OF DERMATOLOGICAL RESEARCH
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2025
·Vol. 317
·期 1
·1-16
·
IF 2.1
Lin Ling,Li Wei,Gao Xinjing,Li Qian,Zhou Xin,Liu Weiyu,Zhong Xuelian,Yang Yunqing,Zhang Xibao,Luo Quan
Psoriasis represents a chronic inflammatory skin disease occurring globally. We investigated the role of plasma exosomal microRNA (miR)- 148a- 3p and its target gene Bim in psoriasis. Plasma exosomes (Exos) and CD4 + T cells were extracted from psoriatic patients. miR- 148a- 3p expression in Exos and CD4 + T cells of psoriatic patients, the proportions of CD4 + T cell subsets, and the contents of anti-inflammatory/pro-inflammatory factors were determined by RT-qPCR, flow cytometry and ELISA. The correlation between plasma exosomal miR- 148a- 3p and CD4 + T cell subsets in psoriatic patients was analyzed by Pearson’s analysis. The psoriatic mouse was treated with Exos/antagomir miR- 148a- 3p. Histopathological changes in the skin were observed. The CD4 + T cell subset levels, serum cytokine contents and miR- 148a- 3p expression in the blood were measured. The miR- 148a- 3p-Bim targeted binding relationship was predicted and verified by Starbase database and dual-luciferase assay. The Bim expression in psoriatic mice was determined. Psoriatic patients had highly-expressed miR- 148a- 3p in both Exos and CD4 + T cells, and abnormal CD4 + T cell subsets and cytokine levels. Plasma exosomal miR- 148a- 3p was correlated with the CD4 + T cell subsets in psoriatic patients. Exos caused down-regulated miR- 148a- 3p level in skin tissues of mouse, regulated CD4 + T cell function and aggravated the symptoms in psoriatic mice. miR- 148a- 3p repression partially reversed the role of Exos in CD4 + T cell function and psoriasis-like symptoms. Exos-carried miR- 148a- 3p targeted Bim in CD4 + T cells of psoriatic mice. Plasma exosomal miR- 148a- 3p targeted Bim to affect the dysfunction of CD4 + T cells in psoriatic mice, thereby aggravating the psoriasis-like symptoms.
研究领域:
皮肤病学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
AUTOIMMUNITY
·
2020
·
IF 2.125
Cao Yongjun,Qiao Nan,Sun Yumeng,Jin Xiaowen,Wen Weibo
Dioscin has been used as a treatment for Hashimoto’s thyroiditis (HT) in China. However, the molecular mechanisms governing the modes of action of dioscin have not been elucidated. In this study, flow cytometry and Western blotting were used to identify the proportions of CD4+CD25+ regulatory T (Treg) cells and the expression of forkhead box P3 (Foxp3) and SUMO-specific protease 1 (SENP1) in HT patients’ peripheral blood mononuclear cells (PBMCs). A pTg-induced rat model of HT was established by injection of 100 μg pTg. Then, the model rats were randomly divided into three groups (n = 5): control (NC), model (HT) and dioscin treatment. After oral administration of dioscin each day for two weeks, CD4+CD25+Foxp3+ Treg cells were analysed by flow cytometry, and the protein expression levels of SENP1, Foxp3, SUMO-1 and SUMO-2/3 were measured by Western blotting. Co-immunoprecipitation (Co-IP) was used to identify the SUMOylation of interferon regulatory factor 4 (IRF4). The results showed that the proportions of CD4+CD25+ Treg cells and the expression of Foxp3 were significantly decreased in HT patients, but the expression of SENP1 was enhanced compared to healthy controls (HCs). However, compared to the pTg-induced HT rat group, the expression of Foxp3, SUMO-1, and SUMO-2/3 and the proportions of CD4+CD25+Foxp3+ Treg cells were increased, whereas the expression of SENP1 was decreased, in the dioscin-treated group. Furthermore, the SUMOylation of IRF4 was increased after SENP1 was knocked down. The results of our study indicate that dioscin can promote the differentiation of the CD4+CD25+Foxp3+ Treg cells and subsequently upregulate the SUMOylation of IRF4 by downregulating SENP1 expression.
研究领域:
免疫学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2025
·
IF 5.4
Junzhu Li,Xin Feng,Yizhi Jing,Haidong Qian,Yun Ji,Yanling Hao,Zhengyuan Zhai
Infectious enteritis is a chronic inflammatory condition of the intestine, mainly characterized by immune cell infiltration and gut microbiota dysbiosis. Resveratrol, a natural polyphenol compound from grapes, berries and peanuts, is known for its antioxidant and anti-inflammatory properties. This study investigated the effects of resveratrol in a murine model of Citrobacter rodentium-induced colitis. Resveratrol ameliorated disease symptoms, body weight loss, colon shortening, and increased intestinal permeability. Histological and immunofluorescence analyses revealed that resveratrol improved intestinal barrier integrity by increasing goblet cells, upregulating MUC-2 expression, reducing crypt hyperplasia, and suppressing epithelial cell apoptosis. Resveratrol significantly decreased the mRNA levels of pro-inflammatory cytokines, namely Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-22 (IL-22), while restoring the percentage of CD4+ cells to normal levels. It also attenuated oxidative stress by enhancing the activities of key antioxidant enzymes, including catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px). Furthermore, resveratrol reshaped the gut microbiota by increasing the abundance of obligate anaerobes Clostridium and decreasing the abundance of facultative anaerobes Enterobacteriaceae. The abundance of Lactobacillus and Dubosiella was also significantly increased by resveratrol. In summary, these findings demonstrate that resveratrol supplementation may serve as a promising nutritional strategy to ameliorate C. rodentium colitis by inhibiting CD4+ cell activation and remodeling the gut microbiota.
研究领域:
微生物组学
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免疫学
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炎症性肠病
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营养免疫
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分子营养学
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肠道屏障功能
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2013
·
IF 3.848
Wu Lian,Mingyi Wu,Ning Huang,Na Gao,Chuang Xiao,Zi Li,Zhigang Zhang,Yongtang Zheng,Wenlie Peng,Jinhua Zhao
Background Fucosylated glycosaminoglycan (FG) is a novel glycosaminoglycan with a chondroitin sulfate-like backbone and fucose sulfate branches. The aim of this study is to investigate the mechanism and structure–activity relationships (SAR) of FG for combating HIV-1 infection. Methods Anti-HIV activities of FGs were assessed by a cytopathic effect assay and an HIV-1 p24 detection assay. The biomolecule interactions were explored via biolayer interferometry technology. The SAR was established by comparing its anti-HIV-1 activities, conserved CD4 induced (CD4i) epitope-dependent interactions and anticoagulant activities. Results FG efficiently and selectively inhibited the X4- and R5X4-tropic HIV-1 infections in C8166 cells with little cytotoxicity against C8166 cells and PBMCs. Our data indicated that FG bound to gp120 with nanomolar affinity and may interact with CD4i of gp120. Additionally, the CD4i binding affinity of FG was higher than that of dextran sulfate. SAR studies suggested that the unique sulfated fucose branches account for the anti-HIV-1 activity. The molecular size and present carboxyl groups of FG may also play important roles in various activities. Notably, several FG derivatives showed higher anti-HIV-1 activities and much lower anticoagulant activities than those of heparin. Conclusions FG exhibits strong activity against X4- and R5X4-tropic HIV-1 infections. The mechanism may be related to targeting CD4i of gp120, which results in inhibition of HIV-1 entry. The carboxyl group substituted derivatives of FG (8.5–12.8 kDa), might display high anti-HIV-1 activity and low anticoagulant activity. General significance Our data supports further the investigation of FG derivatives as novel HIV-1 entry inhibitors targeting CD4i.
研究领域:
病毒学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CELL
·
2019
·
IF 36.216
Ke-qi Fan,Yi-yuan Li,Hao-li Wang,Xin-tao Mao,Jin-xin Guo,Fei Wang,Ling-jie Huang,Yi-ning Li,Xiang-yu Ma,Zheng-jun Gao,Wei Chen,Dan-dan Qian,Wen-jin Xue,Qian Cao,Lei Zhang,Li Shen,Long Zhang,Chao Tong,Jiang-yan Zhong,Wei Lu,Ling Lu,Ke-ming Ren,Guisheng Zhong,Yuan Wang,Mingliang Tang,Xin-Hua Feng,Ren-jie Chai,Jin Jin
Summary Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4 + T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4 + T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4 + T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4 + T cells. Our study implicates a critical link between a purine metabolic disorder in CD4 + T cells and stress-driven anxiety-like behavior.
研究领域:
免疫学
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神经科学
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分子生物学
·
行为科学
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DOI
PubMed
高影响因子
GENOMICS
·
2024
·
IF 3.4
Jiongxue Chen,Jiatian Xie,Fuyin Deng,Jinhua Cai,Sitai Chen,Xingrong Song,Shangzhou Xia,Qingyu Shen,Xinying Guo,Yamei Tang
The significance of the adaptive immune response in Alzheimer's disease (AD) is increasingly recognized. We analyzed scRNA-Seq data from AD patients, revealing a notable rise in CD4 cytotoxic T cells (CD4-CTLs) in peripheral blood mononuclear cells (PBMCs), validated in vivo and in vitro. This rise correlates with cognitive decline in AD patients. We also identified transcription factors TBX21 and MYBL1 as key drivers of CD4-CTL expansion. Further analyses indicate these cells are terminally differentiated, showing clonal expansion, metabolic changes, and unique communication patterns. Mendelian randomization identified risk genes SRGN and ITGB1, suggesting their genetic regulation in CD4-CTLs may contribute to AD. To summarize, our findings characterize the expansion of CD4-CTLs in the PBMCs of AD patients, providing valuable understanding into the possible mechanisms involved in the expansion of CD4-CTLs in AD.
研究领域:
神经科学
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免疫学
·
基因组学
·
转化医学
✓ 已验证
DOI
PubMed
高影响因子
Mucosal Immunology
·
2024
·
IF 7.9
Jinzhe Tong,Simiao Chen,Xinyue Gu,Xuanqi Zhang,Fang Wei,Yingying Xing
Tissue-resident memory T cells (T RM ) can be induced by infection and vaccination, and play a key role in maintaining long-term protective immunity against mucosal pathogens. Our studies explored the key factors and mechanisms affecting the differentiation, maturation, and stable residence of gastric epithelial CD4 + T RM induced by Helicobacter pylori (Hp) vaccine and optimized Hp vaccination to promote the generation and residence of T RM .CD38 regulated mitochondrial activity and enhanced TGF-β signal transduction to promote the differentiation and residence of gastric epithelial CD4 + T RM by mediating the expression of CD105. Extracellular nucleotides influenced the long-term maintenance of T RM in gastric epithelium by P2RX7. Vitamin D3 and Gram-positive enhancer matrix particles (GEMs)as immune adjuvants combined with Hp vaccination promoted the production of CD69 + CD103 + CD4 + T RM .
研究领域:
免疫学
·
微生物学
·
分子生物学
·
疫苗学
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DOI
PubMed
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2016
·Vol. 120
·期 6
·560-570
·
IF 3.097
Hongjun Zhang,Baoling Ju,Xiaoli Zhang,Yanfei Zhu,Ying Nie,Yuanhong Xu,Qiuxia Lei
Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis , which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo . In response to ConA stimulation, the CD4 + T cells preferred to polarizing towards CD4 + T helper 17 (Th17) cells in liver. Magnolol was observed to inhibit Th17 cell differentiation in ConA-treated liver in addition to suppressing interleukin (IL)-17A generation. Hepatic stellate cells were activated in fibrotic liver as demonstrated by increased alpha smooth muscle actin (α-SMA) and desmin. More transforming growth factor (TGF)-β1 and activin A were secreted into the serum. Magnolol suppressed this abnormal HSC activation. Furthermore, the phosphorylation of Smad3 in its linker area (Thr179, Ser 204/208/213) was inhibited by magnolol. In vitro , the recombinant IL-17A plus TGF-β1 or activin A induced activation of human LX2 HSCs and promoted their collagen production. Smad3/Smad4 signalling pathway was activated in LX2 cells exposed to the fibrotic stimuli, as illustrated by the up-regulated phospho-Smad3 and the enhanced interaction between Smad3 and Smad4. These alterations were suppressed by magnolol. Collectively, our study reveals a novel antifibrotic effect of magnolol on Th17 cell-mediated fibrosis.
研究领域:
药理学
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免疫学
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肝病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2023
·Vol. 20
·期 1
·1-15
·
IF 9.3
Zheng Yingxia,Chen Zheyi,Zhou Bingqian,Chen Shiyu,Chen Ningdai,Shen Lisong
Background Protein arginine methyltransferase 5 (Prmt5) is the main type II methyltransferase, catalyzes protein arginine residue symmetric dimethylation, and modulates normal cellular physiology and disease progression. Prmt5 inhibition or deletion in CD4+ T cells has been reported to ameliorate experimental autoimmune encephalomyelitis (EAE), but the detailed molecular mechanisms have not yet been elucidated.Methods EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35–55) in T cells Prmt5 conditional knockout (CD4-cre-Prmt5fl/fl, Prmt5cko) and Prmt5fl/fl (WT) mice. Flow cytometry, single-cell RNA sequencing, ATAC sequencing and chromatin immunoprecipitation assay (ChIP) approaches were used to explore the detail mechanisms.Results We find that Prmt5cko mice are resistant to EAE; infiltrating inflammatory CD4+ T cells in the central nervous system (CNS) are greatly reduced. However, in Prmt5cko mice, T cells in the spleen show much more proliferation and activation properties, the total number of CD4+ T cells in the spleen is not reduced, and the percentage of Rora+ CD4+ T cells is elevated. Also, CD4+ T cells express lower levels of S1pr1 and Klf2 than WT mice, which may influence pathogenic CD4+ T-cell egress from the spleen and migration to the CNS. Moreover, the single-cell ATAC sequence and ChIP assay reveal that the transcription factor Klf2 is enriched at the S1pr1 promoter and that Klf2 motif activity is reduced in Prmt5cko mice.Conclusion sOur study delineates the undiscovered role of Prmt5 in T-cell biology in which Prmt5 may inhibit Klf2-S1pr1 pathway to ameliorate EAE disease. Controlling T-cell Prmt5 expression may be helpful for the treatment of autoimmune diseases.
研究领域:
免疫学
·
分子生物学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Xun He,Jingsong Liu,Yugang Gong,Wei Lu,Xiaowei Sha,Chang Cao,Yanqun Li,Jiawei Wang
Background Evidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. Purpose Therefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. Study design The C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). Methods The optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4 + CD25 + FOXP3 + , CD4 + and CD8 + of skin tissue. And the levels of CD4 + and CD8 + , p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. Results Compared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4 + CD25 + FOXP3 + and CD4 + cells, while inhibited the number of CD8 + positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. Conclusion Amygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway.
研究领域:
药理学
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免疫学
·
皮肤科
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2025
·
IF 3.1
Li Xue,Wang Rui,Ma Xiaonan,Yang Jin,Zhang Shen,Zhang Zimeng,Jiang Han,Liu Jihua,Yu Boyang,Dai Wenling
Effective drugs for neuropathic pain are urgently needed. Natural compound glaucine from Corydalis Rhizoma inhibits spinal sensitization and alleviates neuropathic pain, yet its exact analgesic mechanism remains unclear. A rat model of neuropathic pain was established via chronic constriction injury (CCI) of the sciatic nerve. Behavioral tests (von Frey and Hargreaves tests) were used to assess neuropathic pain symptoms by evaluating mechanical allodynia and thermal hyperalgesia. Primary spinal neurons, glia, and peritoneal macrophages were cultured for in vitro analysis. Molecular pathways were examined using RNA sequencing, Western blot, qRT-PCR, and immunofluorescence. Glaucine significantly suppressed spinal IL-16 expression in CCI rats, and its analgesic effects were reversed by exogenous IL-16 administration. RNA-seq and protein assays confirmed IL-16 upregulation in injured peripheral nerves and spinal cord. Critically, inhibiting IL-16/CD4 signaling at peripheral and spinal levels alleviated neuropathic pain. Dual immunofluorescence in vivo and in vitro revealed IL-16/CD4 localization in neurons, and spinal IL-16 inhibition reduced neuronal activation. Calcium fluorescence imaging further demonstrated that spinal IL-16 blockade reduced spinal neuronal excitability through restraining the NMDA receptor. The IL-16 induced phosphorylation of NMDA receptor was mediated by lymphocyte-specific protein tyrosine kinase (p56 lck ). Additionally, peripheral macrophages were identified as a source of IL-16 after nerve injury. Glaucine alleviates neuropathic pain by inhibiting the IL-16-p56 lck -NMDA axis which promotes pain through enhanced NMDA activity and central sensitization. The targeted inhibition highlights glaucine as a novel therapeutic strategy for alleviating neuropathic pain.
研究领域:
神经药理学
·
疼痛研究
·
分子信号传导
·
免疫神经学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2018
·
IF 5.511
Chen Haiming,Liu Huazhen,Lu Chuanjian,Wang Maojie,Li Xiong,Zhao Hui,Yan Yuhong,Yu Wanling,Han Ling,Dai Zhenhua
Psoriasis is an autoimmune and inflammatory disease, which is estimated to affect 2–3% of the population in the world. PSORI-CM02 is an empirical formula of Chinese medicine optimized from Yin Xie Ling, which is widely used to treat psoriasis in China for decades. However, its antipsoriatic mechanisms are still not well understood. Here, we explored the therapeutic effects of PSORI-CM02 on psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse models and human HaCaT cells. In experiments in vitro, PSORI-CM02 significantly inhibited HaCaT cell proliferation in dose-dependent and time-dependent manners. Furthermore, it hindered the progression of HaCaT cell cycle and arrested HaCaT cells at G1 phase. On the other hand, our in vivo studies demonstrated that PSORI-CM02 dramatically reduced psoriasis area and severity index scores and lesion temperature in imiquimod-induced psoriatic mice. The antioxidative activities of glutathione, catalase, and superoxide dismutase were increased while oxidative activity of malonaldehyde was markedly decreased after treatments with PSORI-CM02. PSORI-CM02 also suppressed the mRNA expression of proinflammatory cytokines, including TNF-α, IL-6, and IL-17, and lowered their protein levels in the serum as well. In addition, PSORI-CM02 could reduce the expression of IKKα and NF-κB in psoriatic skin tissue. It also upregulated the proportion of CD4+ Foxp3+ regulatory T cells (Tregs) in both lymph nodes and spleens and promoted CD4+ CD25+ Treg proliferation in vitro. Taken together, our research demonstrated that PSORI-CM02 inhibited HaCaT cell proliferation by arresting them at G1 phase and alleviated systemic inflammation and psoriasis in mice via altering the oxidative/anti-oxidative status, tipping the balance between Th17 responsiveness and CD4+ Foxp3+ Treg generation, and suppressing the expression of proinflammatory cytokines as well as NF-κB signaling.
研究领域:
免疫学
·
药理学
·
皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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