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https://www.readbyqxmd.com/read/29332158/combined-sublethal-irradiation-and-agonist-anti-cd40-enhance-donor-t-cell-accumulation-and-control-of-autochthonous-murine-pancreatic-tumors
#1
Lindsay K Ward-Kavanagh, Kathleen M Kokolus, Timothy K Cooper, Aron E Lukacher, Todd D Schell
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells...
January 13, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29330524/nf-%C3%AE%C2%BAb-inducing-kinase-is-a-therapeutic-target-for-systemic-lupus-erythematosus
#2
Hans D Brightbill, Eric Suto, Nicole Blaquiere, Nandhini Ramamoorthi, Swathi Sujatha-Bhaskar, Emily B Gogol, Georgette M Castanedo, Benjamin T Jackson, Youngsu C Kwon, Susan Haller, Justin Lesch, Karin Bents, Christine Everett, Pawan Bir Kohli, Sandra Linge, Laura Christian, Kathy Barrett, Allan Jaochico, Leonid M Berezhkovskiy, Peter W Fan, Zora Modrusan, Kelli Veliz, Michael J Townsend, Jason DeVoss, Adam R Johnson, Robert Godemann, Wyne P Lee, Cary D Austin, Brent S McKenzie, Jason A Hackney, James J Crawford, Steven T Staben, Moulay H Alaoui Ismaili, Lawren C Wu, Nico Ghilardi
NF-κB-inducing kinase (NIK) mediates non-canonical NF-κB signaling downstream of multiple TNF family members, including BAFF, TWEAK, CD40, and OX40, which are implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we show that experimental lupus in NZB/W F1 mice can be treated with a highly selective and potent NIK small molecule inhibitor. Both in vitro as well as in vivo, NIK inhibition recapitulates the pharmacological effects of BAFF blockade, which is clinically efficacious in SLE...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29329699/soluble-cd40-ligand-disrupts-the-blood-brain-barrier-and-exacerbates-inflammation-in-experimental-autoimmune-encephalomyelitis
#3
Hiroki Masuda, Masahiro Mori, Kenta Umehara, Tomomi Furihata, Tomohiko Uchida, Akiyuki Uzawa, Satoshi Kuwabara
Serum soluble CD40 ligand (sCD40L) has been reported to positively correlate with the albumin quotient, a marker of blood-brain barrier (BBB) breakdown, in patients with multiple sclerosis (MS). To clarify the mechanisms of sCD40L in MS pathophysiology, sCD40L was administered to experimental autoimmune encephalomyelitis (EAE) mice and a human brain microvascular endothelial cell (HBMEC)-based BBB model. The high-dose sCD40L group showed a worse EAE score than the low-dose and control groups. BBB permeability was increased by administering sCD40L in a HBMEC-based BBB model...
January 3, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29325864/infections-genetic-and-environmental-factors-in-pathogenesis-of-autoimmune-thyroid-diseases
#4
REVIEW
Sanjeev Kumar Shukla, Govind Singh, Shahzad Ahmad, Prabhat Pant
In Autoimmune disease a combination of infection, genetic and environmental factors causes an autoimmune response to the thyroid gland (characterized by lymphocytic infiltrations), thyroid stimulating hormone receptor (TSHR) and different thyroid antigens. Graves' and Hashimoto disease are autoimmune disorders with genetic predisposition. CD40 that stimulates the proliferation and differentiation of lymphocytes is an essential immunomodulatory component for follicular cells in the thyroid and the cell that present the antigen...
January 8, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29324305/caveolin-mediated-endocytosis-of-the-chlamydia-m278-outer-membrane-peptide-encapsulated-in-poly-lactic-acid-poly-ethylene-glycol-nanoparticles-by-mouse-primary-dendritic-cells-enhances-specific-immune-effectors-mediated-by-mhc-class-ii-and-cd4-t-cells
#5
Saurabh Dixit, Rajnish Sahu, Richa Verma, Skyla Duncan, Guillermo H Giambartolomei, Shree R Singh, Vida A Dennis
We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules...
December 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/29321275/cd40-mediates-maturation-of-thymic-dendritic-cells-driven-by-self-reactive-cd4-thymocytes-and-supports-development-of-natural-regulatory-t-cells
#6
Jaehak Oh, Nan Wu, Andrea J Barczak, Rebecca Barbeau, David J Erle, Jeoung-Sook Shin
Thymic dendritic cells (tDCs) play an important role in central tolerance by eliminating self-reactive thymocytes or differentiating them to regulatory T (Treg) cells. However, the molecular and cellular mechanisms underlying these functions are not completely understood. We found that mouse tDCs undergo maturation following cognate interaction with self-reactive CD4+ thymocytes and that this maturation is dependent on CD40 signaling. Ablation of CD40 expression in tDCs resulted in a significant reduction in the number of Treg cells in association with a significant reduction in the number of mature tDCs...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29319621/selective-cd28-inhibition-modulates-alloimmunity-and-cardiac-allograft-vasculopathy-in-anti-cd154-treated-monkeys
#7
Tianshu Zhang, Agnes M Azimzadeh, Wenji Sun, Natalie A O'Neill, Evelyn Sievert, Emily Bergbower, Gheorghe Braileanu, Lars Burdorf, Xiangfei Cheng, Thomas Monahan, Siamak Dahi, Donald Harris, Elana Rybak, Emily Welty, Anthony Kronfli, Chris Avon, Richard N Pierson
BACKGROUND: Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade...
January 10, 2018: Transplantation
https://www.readbyqxmd.com/read/29309879/anti-nociceptive-role-of-cxcl1-in-a-murine-model-of-peripheral-nerve-injury-induced-neuropathic-pain
#8
Ling Cao, Jennifer T Malon
Both spinal cord infiltrating CD4+ T lymphocytes and microglial CD40 contribute to the maintenance of neuropathic pain-like behaviors induced by spinal nerve L5 transection (L5Tx), a murine model of neuropathic pain. Here, we sought to investigate the involvement of multiple chemokines in microglial CD40-mediated and CD4+ T lymphocytes-mediated L5Tx-induced sensory hypersensitivity. Spinal cord chemokine expression in CD4 knockout (KO), CD40 KO, and wild type (WT) BALB/c mice was determined at the protein level via multiplex assays and at the RNA level via quantitative real-time PCR...
January 5, 2018: Neuroscience
https://www.readbyqxmd.com/read/29308628/induction-of-apoptosis-in-cancer-cells-of-pre-b-all-patients-after-exposure-to-platelets-platelet-derived-microparticles-and-soluble-cd40-ligand
#9
Morteza Yaftian, Fatemeh Yari, Mehran Ghasemzadeh, Vahid Fallah Azad, Mansoureh Haghighi
OBJECTIVES: The in vitro treatment of tumor cells with platelet (Plt) causes inhibition of tumor cell growth, although mechanism of this effect is not clear yet. Induction of apoptosis has been proposed as a mechanism of Plt effects on tumor cells. The purpose of this study was to clarify the role of Plts and Plt-derived components in the induction of apoptosis in the blood mononuclear cells of patients with leukemia. MATERIALS AND METHODS: In this experimental study, peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of five patients with childhood B-precursor acute lymphoblastic leukemia (pre-B ALL) and encountered with Plts, Plt-derived microparticles (Plt-MPs) as well as purified soluble CD40L (sCD40L)...
April 2018: Cell Journal
https://www.readbyqxmd.com/read/29308304/pd-1-related-transcriptome-profile-and-clinical-outcome-in-diffuse-gliomas
#10
Shuai Liu, Zheng Wang, Yinyan Wang, Xing Fan, Chuanbao Zhang, Wenbin Ma, Xiaoguang Qiu, Tao Jiang
Background: PD-1 plays a critical part in control of immune response to malignancy. Anti-PD-1 treatment is a hopeful strategy to improve the dismal prognosis of gliomas. To characterize the role of PD-1 in diffuse gliomas, we investigated its related biological process at transcriptome level and its clinical prognostic value. Method and patients: Through Chinese Glioma Genome Atlas and TCGA datasets, we systematically reviewed a total of 994 cases with RNA-seq data and analyzed the functional annotation of PD-1 by Gene ontology (GO) analysis...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29306404/cerebrospinal-fluid-pentraxin-3-and-cd40-ligand-in-anti-n-menthyl-d-aspartate-receptor-encephalitis
#11
Baozhu Liu, Peiying Ai, Dong Zheng, Ying Jiang, Xiaojia Liu, Suyue Pan, Honghao Wang
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system whose pathogenesis involves interleukin (IL)-6 and IL-17A. We examined the correlations between CSF concentrations of the acute-phase protein pentraxin 3 (PTX3), the chronic inflammatory mediator CD40L, IL-6, and IL-17A in anti-NMDAR encephalitis, and the impact on clinical outcome. PTX3, CD40L, IL-6, and IL-17A were significantly higher in the CSF of patients with anti-NMDAR encephalitis than in controls...
February 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29303623/x-linked-hyper-igm-syndrome-a-phenotype-of-crohn-s-disease-with-hemophagocyticlymphohistiocytosis
#12
Kun-Yin Qiu, Xiong-Yu Liao, Ruo-Hao Wu, Ke Huang, Jian-Pei Fang, Dun-Hua Zhou
X-linked hyper-immunoglobulin M (IgM) syndrome is characterized by recurrent infections, low or undetectable levels of IgG and IgA, and normal to increased serum IgM, and is also rare. It is associated with mutation in the gene encoding CD40 ligand. This study aimed to describe the first international report of hemizygous CD40LG c.542G>A mutation in a 5-year-old boy with a phenotype of Crohn's disease and hemophagocyticlymphohistiocytosis. Also, the clinical implications of this mutation and associated atypical phenotype are discussed...
January 5, 2018: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29302052/the-act1-d10n-missense-variant-impairs-cd40-signaling-in-human-b-cells
#13
Ning Yu, Sylviane Lambert, Joshua Bornstein, Rajan P Nair, Charlotta Enerbäck, James T Elder
The TRAF3IP2 gene resides within one of at least 63 psoriasis susceptibility loci and encodes Act1, an adapter protein involved in IL-17 receptor and CD40 signaling pathways. TRAF3IP2 is distinctive (among <10% of candidate susceptibility genes) in that a strongly disease-associated variant encodes a missense SNP predicted to be functionally relevant (SNP rs33980500 C/T encoding Act1 pD10N). As assessed by flow cytometry, Act1 protein was expressed at the highest levels in monocytes, with lower levels in T-cells and B-cells...
January 5, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29296923/the-oncogenic-membrane-protein-lmp1-sequesters-traf3-in-b-cell-lymphoma-cells-to-produce-functional-traf3-deficiency
#14
Pradeep Bangalore-Prakash, Laura L Stunz, Nurbek Mambetsariev, Amy L Whillock, Bruce S Hostager, Gail A Bishop
Loss-of-function mutations in genes encoding the signaling protein tumor necrosis factor receptor-associated factor 3 (TRAF3) are commonly found in human B-cell malignancies, especially multiple myeloma and B-cell lymphoma (BCL). B-cell TRAF3 deficiency results in enhanced cell survival, elevated activation receptor signaling, and increased activity of certain transcriptional pathways regulating expression of prosurvival proteins. A recent analysis of TRAF3 protein staining of ∼300 human BCL tissue samples revealed that a higher proportion of samples expressing the oncogenic Epstein-Barr virus-encoded protein latent membrane protein 1 (LMP1) showed low/negative TRAF3 staining than predicted...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288900/increased-pd-1-cd154-tfh-cells-are-possibly-the-most-important-functional-subset-of-pd-1-t-follicular-helper-cells-in-adult-patients-with-minimal-change-disease
#15
Tao Li, Yunpeng Shi, Weixia Sun, Haifeng Wang, Quan Wang, Yanfang Jiang
T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1)+ Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1+ Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1+, PD-1+CD154+, and PD-1+interleukin (IL)-21+ Tfh cells, and CD38+CD19+ and CD38+CD19+CD40+ B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-γ were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0...
December 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29276180/cd40-knocked-down-tolerogenic-dendritic-cells-decrease-diabetic-injury
#16
Aziz Mahmoudzadeh, Ali Akbar Pourfathollah, Mohammad Hossein Karimi, Seyed Mohammad Moazzeni
BACKGROUND: Type-1 diabetes (T1D) is an autoimmune disease in which T lymphocytes destroy insulin-producing β-cells. Control of self-reactive T lymphocytes and recovery of diabetic injury is the end point of T1D. OBJECTIVE: To investigate generation of tolerogenic dendritic cells (tolDCs) as an innovative method of diabetes therapy. METHODS: Lentivirus vector production was achieved by GIPZ mouse CD40 shRNA, psPAX2 and pMD2G plasmids DNA...
December 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/29260516/-effect-of-recombinant-antigen-ferritin-on-dc-induce-immune-response
#17
Ya-Na Wang, Qiang Wang, Chan Wang, Wei Zhao
OBJECTIVE: To explore the immunoreaction against protoscolex infection by the recombinant ferritin of echinococcus granulosus (rEg.ferritin) immunized mice. METHODS: Bone marrow deriedstem cells (BMDCs) were collected and exposed in different antigens by cell culture and included 6 groups,there were hydatid fluid (HF) group (HF 30 μg/mL),rEg.ferritin group (rEg.ferritin 1 μg/mL), rEg.ferritin+LPS group (rEg.ferritin 1 μg/mL and LPS 100 ng/mL),HF+LPS group (HF 30 μg/mL and LPS 100 ng/mL),LPS group (LPS 100 ng/mL) and control (not add antigen)...
November 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29250828/cd4-cd25hi-foxp3-regulatory-t-cells-in-long-term-cardiac-xenotransplantation
#18
Avneesh K Singh, Joshua L Chan, Caleb N Seavey, Philip C Corcoran, Robert F Hoyt, Billeta G T Lewis, Marvin L Thomas, David L Ayares, Keith A Horvath, Muhammad M Mohiuddin
BACKGROUND: CD4+CD25Hi FoxP3+ T (Treg) cells are a small subset of CD4+ T cells that have been shown to exhibit immunoregulatory function. Although the absolute number of Treg cells in peripheral blood lymphocytes (PBL) is very small, they play an important role in suppressing immune reactivity. Several studies have demonstrated that the number of Treg cells, rather than their intrinsic suppressive capacity, may contribute to determining the long-term fate of transplanted grafts. In this study, we analyzed Treg cells in PBL of long-term baboon recipients who have received genetically modified cardiac xenografts from pig donors...
December 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29249591/relationship-between-cardiac-troponin-and-thrombo-inflammatory-molecules-in-prediction-of-outcome-after-acute-ischemic-stroke
#19
Peter Csecsei, Gabriella Pusch, Erzsebet Ezer, Timea Berki, Laszlo Szapary, Zsolt Illes, Tihamer Molnar
BACKGROUND: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers. METHODS: Thirty-five patients with first-ever AIS were prospectively examined. Serum hs-cTnT was measured 6 and 24 hours after stroke, whereas S100B, high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand, tissue plasminogen activator (tPA), monocyte chemoattractant protein-1 (MCP-1), and P-selectin were measured 6 and 72 hours after stroke...
December 14, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29248792/crocin-alleviates-coronary-atherosclerosis-via-inhibiting-lipid-synthesis-and-inducing-m2-macrophage-polarization
#20
Jing Li, Hong-Tao Lei, Lei Cao, Yan-Ni Mi, Sen Li, Yong-Xiao Cao
Atherosclerosis is a chronic inflammatory disease arising from an imbalance in lipid levels and the accumulation of cholesterol-laden macrophages in the artery wall. Crocin is an active ingredient of Crocus sativus L. This study established a rat coronary atherosclerosis model induced by vitamin D3 (VD3), to explore the effect of Crocin on lipid metabolism, macrophage polarization and the activity of inflammatory proteins. The results revealed that Crocin decreased blood lipid levels by decreasing the levels of endothelin (ET), total cholesterol (TC), triglyceridelow (TG) and low-density lipoprotein cholesterol (LDL-c), elevating the level of high-density lipoprotein cholesterin (HDL-c)...
December 14, 2017: International Immunopharmacology
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