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https://www.readbyqxmd.com/read/29345060/porcine-nk-cells-display-features-associated-with-antigen-presenting-cells
#1
Steffi De Pelsmaeker, Bert Devriendt, Georges Leclercq, Herman W Favoreel
NK cells are members of the innate immunity and play a central role in the defense against viral infections and cancer development, but also contribute to triggering and shaping adaptive immune responses. Human NK cells may express MHC II and costimulatory molecules, including CD86, CD80, and OX40 ligand, which allows them to stimulate the CD4+ T-cell response. In contrast, murine NK cells do not express MHC II or costimulatory molecules. Upon activation, mouse NK cells can acquire these molecules from dendritic cells (DCs) via intercellular membrane transfer, which leads to suppression of DC-induced CD4+ T-cell responses rather than stimulation of T-cell responses...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344664/crucial-role-of-ox40-ox40l-signaling-in-a-murine-model-of-asthma
#2
Wei Lei, Daxiong Zeng, Gaoqin Liu, Yehan Zhu, Jiajia Wang, Hongya Wu, Junhong Jiang, Jianan Huang
The aim of the present study was to explore the roles of OX40/OX40 ligand (OX40L) signaling and OX40+ T cells in ovalbumin (OVA)‑induced mouse asthma model. Asthma was induced by OVA exposure and subsequent co‑treatment with OX40L protein, neutralizing anti‑OX40L blocking antibody, OX40+ T cells or PBS. The protein expression levels of interleukin (IL)‑4, IL‑6, IL‑13, IL‑17, tumor necrosis factor (TNF)‑α and interferon (IFN)‑γ in bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific ELISA...
January 18, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29339447/guidance-of-super-enhancers-in-regulation-of-il-9-induction-and-airway-inflammation
#3
Xiang Xiao, Yihui Fan, Junhui Li, Xiaolong Zhang, Xiaohua Lou, Yaling Dou, Xiaomin Shi, Peixiang Lan, Yue Xiao, Laurie Minze, Xian Chang Li
Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29330524/nf-%C3%AE%C2%BAb-inducing-kinase-is-a-therapeutic-target-for-systemic-lupus-erythematosus
#4
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/29330050/production-and-characterization-of-a-novel-site-specific-modifiable-anti-ox40-receptor-single-chain-variable-fragment-for-targeted-drug-delivery
#5
Aki Tanabe, Kazumi Nakano, Makoto Nakakido, Satoru Nagatoishi, Yuetsu Tanaka, Kouhei Tsumoto, Kaoru Uchimaru, Toshiki Watanabe
OX40 receptor (tumor necrosis factor receptor superfamily, member 4; CD134) is a T-cell co-stimulatory molecule that plays an important role in T-cell activation and survival. OX40 receptor is activated by its ligand, OX40L; and modulation of the OX40-OX40L interaction is a promising target for the treatment of autoimmune diseases and cancers. Here, we generated a high-affinity anti-OX40 single-chain variable fragment carrying a C-terminal cysteine residue (scFvC). Physicochemical and functional analyses revealed that the scFvC bound to OX40-expressing cells and was internalized via OX40-mediated endocytosis without inducing phosphorylation of IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), an important complex in the classical NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29321210/the-immune-checkpoint-modulator-ox40-and-its-ligand-ox40l-in-nk-cell-immunosurveillance-and-acute-myeloid-leukemia
#6
Tina Nuebling, Carla Emilia Schumacher, Martin Hofmann, Ilona Hagelstein, Benjamin Joachim Schmiedel, Stefanie Maurer, Birgit Federmann, Kathrin Rothfelder, Malte Roerden, Daniela Dorfel, Pascal Schneider, Gundram Jung, Helmut Rainer Salih
The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly, these cells are being clinically evaluated for cancer treatment through multiple approaches, such as adoptive transfer of ex vivo expanded polyclonal NK cells (pNKC). Here we analyzed whether and how OX40 and its ligand (OX40L) influence NK-cell function and anti-leukemia reactivity...
January 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29313971/in-vivo-antitumor-function-of-tumor-antigen-specific-ctls-generated-in-the-presence-of-ox40-co-stimulation-in-vitro
#7
Ngoc Pham Minh, Satoshi Murata, Naomi Kitamura, Tomoyuki Ueki, Masatsugu Kojima, Toru Miyake, Katsushi Takebayashi, Hirokazu Kodama, Eiji Mekata, Masaji Tani
Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine...
January 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29311309/signaling-by-the-epstein-barr-virus-lmp1-protein-induces-potent-cytotoxic-cd4-and-cd8-t-cell-responses
#8
Il-Kyu Choi, Zhe Wang, Qiang Ke, Min Hong, Yu Qian, Xiujuan Zhao, Yuting Liu, Hye-Jung Kim, Jerome Ritz, Harvey Cantor, Klaus Rajewsky, Kai W Wucherpfennig, Baochun Zhang
The B-lymphotropic Epstein-Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and a smaller expansion of CD4+ cells. A major approach to treating EBV-associated lymphomas is adoptive transfer of autologous or allogeneic T cells that are stimulated/expanded on EBV-transformed B cells...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29310423/phloxine-o-a-cosmetic-colorant-suppresses-the-expression-of-thymic-stromal-lymphopoietin-and-acute-dermatitis-symptoms-in-mice
#9
Hye Eun Lee, Gabsik Yang, Kyu-Bong Kim, Byung-Mu Lee, Joo Young Lee
Cosmetics are primarily applied to the skin; therefore, the association of cosmetic dyes with skin diseases or inflammation is a topic of great interest. Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine that activates dendritic cells to promote Th2 inflammatory immune responses. TSLP is highly expressed in keratinocytes under inflammatory conditions, which suggests that it may play a critical role in the development of skin diseases, such as atopic dermatitis. Therefore, we investigated whether cosmetic dyes influenced the production of TSLP by keratinocytes...
January 9, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29305519/antigen-specific-antitumor-responses-induced-by-ox40-agonist-are-enhanced-by-ido-inhibitor-indoximod
#10
Zuzana Berrong, Mikayel Mkrtichyan, Shamim Ahmad, Mason Webb, Eslam Mohamed, Grigori Okoev, Adelaida Matevosyan, Rajeev Shrimali, Rasha Abu Eid, Scott Hammond, John E Janik, Samir N Khleif
Although an immune response to tumors may be generated using vaccines, so far, this approach has only shown minimal clinical success. This is attributed to the tendency of cancer to escape immune surveillance via multiple immune suppressive mechanisms. Successful cancer immunotherapy requires targeting these inhibitory mechanisms along with enhancement of antigen-specific immune responses to promote sustained tumor-specific immunity. Here we evaluated the effect of indoximod, an inhibitor of the immunosuppressive indoleamine-(2,3)-dioxygenase (IDO) pathway, on antitumor efficacy of anti-OX40 agonist in the context of vaccine in the IDO- TC-1 tumor model...
January 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29305435/an-immunotherapeutic-cd137-agonist-releases-eomesodermin-from-thpok-repression-in-cd4-t-cells
#11
Payal Mittal, Rebecca Abblett, Joseph M Ryan, Adam T Hagymasi, Archibald Agyekum-Yamoah, Julia Svedova, Steven L Reiner, Marie-Clare St Rose, Matthew P Hanley, Anthony T Vella, Adam J Adler
Agonists to the TNF/TNFR costimulatory receptors CD134 (OX40) and CD137 (4-1BB) elicit antitumor immunity. Dual costimulation with anti-CD134 plus anti-CD137 is particularly potent because it programs cytotoxic potential in CD8+ and CD4+ T cells. Cytotoxicity in dual-costimulated CD4 T cells depends on the T-box transcription factor eomesodermin (Eomes), which we report is induced via a mechanism that does not rely on IL-2, in contrast to CD8+ CTL, but rather depends on the CD8 T cell lineage commitment transcription factor Runx3, which supports Eomes expression in mature CD8+ CTLs...
January 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29248519/t-cell-inhibitors-for-atopic-dermatitis
#12
W James Tidwell, Joseph F Fowler
The management of atopic dermatitis is changing with the development of novel biological agents to target specific molecules in the inflammatory cascade. Dupilumab has proven its ability to act on the IL-4 receptor in treating atopic dermatitis. Thymic stromal lymphopoietin (TSLP) monoclonal antibody (AMG157/ MEDI9929) and OX40 blocking antibody (GBR 830) were developed by target the same pathway as dupilumab. The clinical data on the efficacy for these drugs is not yet known. There is some early evidence that AMG157/ MEDI9929 attenuates most measures of allergen-induced asthmatic responses...
December 14, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29244194/arid5a-stabilizes-ox40-mrna-in-murine-cd4-t-cells-by-recognizing-a-stem-loop-structure-in-its-3-utr
#13
Hamza Hanieh, Kazuya Masuda, Hozaifa Metwally, Jaya P Chalise, Maged Mohamed, Kishan K Nyati, Daron M Standley, Songling Li, Mitsuru Higa, Mohammad M Zaman, Tadamitsu Kishimoto
AT-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) required for autoimmunity via stabilization of interleukin-6 (Il6) and signal transducer and activator of transcription 3 (STAT3) mRNAs. However, the roles of Arid5a in Th17 cells and its association with autoimmunity remains unknown. Here, we show that the levels of Arid5a and OX40 are correlated in CD4+ T cells under Th17 conditions in an IL-6-dependent manner. Lack of Arid5a in T cells reduced OX40 expression levels and repressed IL-17 production in response to OX40 ligation...
December 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29228688/altered-follicular-helper-t-cell-impaired-antibody-production-in-a-murine-model-of-myelodysplastic-syndromes
#14
Huijuan Jiang, Ningbo Cui, Liyan Yang, Chunyan Liu, Lanzhu Yue, Lifang Guo, Huaquan Wang, Zonghong Shao
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic diseases which have a high risk of progressing to acute myeloid leukemia. MDS patients have immunologic deficiency, including T and B cells dysfunction. Follicular T helper cells (Tfh, CD4+CXCR5+) are an important subset of helper T cells which help to the formation of germinal centers and B cells differentiation. In this study, we investigated the proportion and function of Tfh using NUP98-HOXD13 transgenic (NHD13) mice model with MDS phenotype...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207606/combination-therapy-with-an-ox40l-fusion-protein-and-a-vaccine-targeting-the-transcription-factor-twist-inhibits-metastasis-in-a-murine-model-of-breast-cancer
#15
Anthony S Malamas, Scott A Hammond, Jeffrey Schlom, James W Hodge
OX40 is a costimulatory receptor that potentiates proliferation, survival, memory formation, and effector function of CD4+ and CD8+ T-cells, while overcoming the suppressive activity of regulatory T-cells (Tregs). Here, we explored the combination of an OX40L fusion protein (OX40L-FP) with a poxvirus-based cancer vaccine (MVA-Twist-TRICOM) to inhibit tumor metastasis in the 4T1 murine breast cancer model. Contrary to the single agent treatments, the combination therapy significantly decreased the number of metastatic colonies per lung and prolonged survival...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151021/regulatory-t-cells-induced-by-b-cells-a-novel-subpopulation-of-regulatory-t-cells
#16
REVIEW
Chien-Hui Chien, Bor-Luen Chiang
Regulatory T cells play a crucial role in the homeostasis of the immune response. In addition to CD4+Foxp3+ regulatory T cells, several subsets of Foxp3- regulatory T cells, such as T helper 3 (Th3) cells and type 1 regulatory T (Tr1) cells, have been described in mice and human. Accumulating evidence shows that naïve B cells contribute to tolerance and are able to promote regulatory T cell differentiation. Naïve B cells can convert CD4+CD25- T cells into CD25+Foxp3- regulatory T cells, named Treg-of-B cells by our group...
November 18, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#17
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29141863/eight-color-multiplex-immunohistochemistry-for-simultaneous-detection-of-multiple-immune-checkpoint-molecules-within-the-tumor-microenvironment
#18
Mark A J Gorris, Altuna Halilovic, Katrin Rabold, Anne van Duffelen, Iresha N Wickramasinghe, Dagmar Verweij, Inge M N Wortel, Johannes C Textor, I Jolanda M de Vries, Carl G Figdor
Therapies targeting immune checkpoint molecules CTLA-4 and PD-1/PD-L1 have advanced the field of cancer immunotherapy. New mAbs targeting different immune checkpoint molecules, such as TIM3, CD27, and OX40, are being developed and tested in clinical trials. To make educated decisions and design new combination treatment strategies, it is vital to learn more about coexpression of both inhibitory and stimulatory immune checkpoints on individual cells within the tumor microenvironment. Recent advances in multiple immunolabeling and multispectral imaging have enabled simultaneous analysis of more than three markers within a single formalin-fixed paraffin-embedded tissue section, with accurate cell discrimination and spatial information...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29141217/th1-like-plasmodium-specific-memory-cd4-t-cells-support-humoral-immunity
#19
Ryan A Zander, Rahul Vijay, Angela D Pack, Jenna J Guthmiller, Amy C Graham, Scott E Lindner, Ashley M Vaughan, Stefan H I Kappe, Noah S Butler
Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29118006/the-immunobiology-of-cd27-and-ox40-and-their-potential-as-targets-for-cancer-immunotherapy
#20
Sarah L Buchan, Anne Rogel, Aymen Al-Shamkhani
In recent years monoclonal antibodies (mAbs) able to reinvigorate anti-tumor T cell immunity have heralded a paradigm shift in cancer treatment. The most high profile of these mAbs block the inhibitory checkpoint receptors PD-1 and CTLA-4 and have improved life expectancy for patients across a range of tumor types. However, it is becoming increasingly clear that failure of some patients to respond to checkpoint inhibition is due to inadequate T-cell priming. For full T-cell activation two signals must be received and ligands providing the second of these signals, termed costimulation, are often lacking in tumors...
November 8, 2017: Blood
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