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https://www.readbyqxmd.com/read/29666503/regulatory-t-cell-derived-extracellular-vesicles-modify-dendritic-cell-function
#1
Sim L Tung, Dominic A Boardman, Monica Sen, Marilena Letizia, Qi Peng, Nicole Cianci, Laura Dioni, Leo M Carlin, Robert Lechler, Valentina Bollati, Giovanna Lombardi, Lesley A Smyth
Regulatory T cells (Treg) are a subpopulation of T cells that maintain tolerance to self and limit other immune responses. They achieve this through different mechanisms including the release of extracellular vesicles (EVs) such as exosomes as shown by us, and others. One of the ways that Treg derived EVs inhibit target cells such as effector T cells is via the transfer of miRNA. Another key target for the immunoregulatory function of Tregs is the dendritic cells (DCs). In this study we demonstrate directly, and for the first time, that miRNAs are transferred from Tregs to DCs via Treg derived EVs...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29660333/epitope-based-ligation-of-icam-1-therapeutic-target-for-protection-against-the-development-of-rheumatoid-arthritis
#2
Jae-Il Lee, Hi-Jung Park, Hye-Jin Park, Yun-Jung Choi, Jiyeon Kim, Jin Kyun Park, Kyeong Cheon Jung, Eung-Soo Hwang, Eun Bong Lee, Seong Hoe Park
Identification of a particular epitope on the domain 2 of human ICAM-1 led us to focus on its role in the treatment of rheumatoid arthritis (RA). Key observations from our previous xenotransplantation research included the generation of tolerogenic DCs, antigen-specific T-cell tolerance, and reduced production of inflammatory cytokines. The critically important point is the fact that it works initially on DC maturation. Ligation of this epitope with a recognizing antibody, MD-3, was also able to create a tolerogenic environment in RA in a manner sililar to that created by xenotransplantation...
April 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29655565/the-tolerogenic-role-of-ifn-%C3%AE
#3
REVIEW
Primož Rožman, Urban Švajger
Due to its extremely pleiotropic nature, the complex effects of IFN-γ exerted both on immune and non-immune cell types still remain only partially understood. The longstanding view of IFN-γ as being a predominantly inflammatory cytokine is constantly challenged by increasing demonstrations of its direct or indirect regulatory roles. Interferon-γ can exert tolerogenic effects on both innate and adaptive immune cell types, promoting tolerance of various antigen-presenting cells, and augmenting function and differentiation of regulatory T cells, respectively...
April 7, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29649510/ilt4-functions-as-a-potential-checkpoint-molecule-for-tumor-immunotherapy
#4
REVIEW
Aiqin Gao, Yuping Sun, Guangyong Peng
Immune checkpoint blockade therapy targeting CTLA4 and PD-1/PD-L1 is a promising strategy in the treatment of different types of cancers. However, the clinical success rates of these therapies are still moderate and varied among cancer types. Therefore, identification of alternative and novel checkpoint molecules or interrupting tolerogenic pathways is urgently needed for successful tumor immunotherapy. Immunoglobulin-like transcript 4 (ILT4) is as an immunosuppressive molecule predominantly expressed in myeloid cells, including monocytes, macrophages, dendritic cells and granulocytes...
April 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29648878/protective-effect-of-lactobacillus-reuteri-dsm-17938-against-experimental-necrotizing-enterocolitis-is-mediated-by-toll-like-receptor-2
#5
Thomas K Hoang, Baokun He, Ting Wang, Dat Q Tran, Jon Marc Rhoads, Yuying Liu
Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to reduce the incidence and severity of necrotizing enterocolitis (NEC). It is unclear if preventing NEC by LR 17938 is mediated by toll-like receptor 2 (TLR2), which is known to mediate pro-inflammatory responses to bacterial cell wall components. NEC was induced in newborn TLR2-/- or WT mice by the combination of gavage-feeding cow milk-based formula and exposure to hypoxia and cold stress. Treatment groups were administered formula supplemented with LR 17938 or placebo (MRS media)...
April 12, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29643856/the-contribution-of-non-professional-antigen-presenting-cells-to-immunity-and-tolerance-in-the-liver
#6
REVIEW
Christina Mehrfeld, Steven Zenner, Miroslaw Kornek, Veronika Lukacs-Kornek
The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical location, it is constantly exposed to microbial and food-derived antigens from the gut and thus equipped with a complex cellular network that ensures dampening T-cell responses. Within this cellular network, parenchymal cells (hepatocytes), non-parenchymal cells (liver sinusoidal endothelial cells and hepatic stellate cells), and immune cells contribute directly or indirectly to this process. Despite this refractory bias, the liver is capable of mounting efficient T-cell responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29643846/lilrb4-decrease-on-udcs-exacerbate-abnormal-pregnancy-outcomes-following-toxoplasma-gondii-infection
#7
Shaowei Zhan, Jing Zheng, Haixia Zhang, Mingdong Zhao, Xianbing Liu, Yuzhu Jiang, Chunyan Yang, Liqin Ren, Zhiqiang Liu, Xuemei Hu
Toxoplasma gondii ( T. gondii ) infection in early pregnancy can result in miscarriage, dead fetus, and other abnormalities. The LILRB4 is a central inhibitory receptor in uterine dendritic cells (uDCs) that plays essential immune-regulatory roles at the maternal-fetal interface. In this study, T. gondii -infected human primary uDCs and T. gondii -infected LILRB4-/- pregnant mice were utilized. The immune mechanisms underlying the role of LILRB4 on uDCs were explored in the development of abnormal pregnancy outcomes following T...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29620252/tim%C3%A2-4-blockade-of-kcs-combined-with-exogenous-tgf%C3%A2-%C3%AE-injection-helps-to-reverse-acute-rejection-and-prolong-the-survival-rate-of-mice-receiving-liver-allografts
#8
Hao Wu, Xuesong Xu, Jinzheng Li, Jianping Gong, Min Li
An acute reaction response (AR) following liver transplantation (LT) is caused by immune responses that are primarily mediated by T lymphocytes. Kupffer cells (KCs) are the largest antigen presenting cell (APC) group in vivo and are the primary modulators of the inflammatory or tolerogenic immune response in liver tissues. T cell immunoglobulin‑domain and mucin‑domain-4 (TIM‑4), the only TIM protein not expressed on T cells, is expressed on APCs; suggesting that it mediates the various immune responses...
March 30, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29616018/induction-of-interleukin-10-producing-dendritic-cells-as-a-tool-to-suppress-allergen-specific-t-helper-2-responses
#9
REVIEW
Stefan Schülke
Dendritic cells (DCs) are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10) is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens to prevent chronic inflammation and tissue damage...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29610286/immunotherapy-for-pancreatic-cancer-more-than-just-a-gut-feeling
#10
Erick Riquelme, Anirban Maitra, Florencia McAllister
<b/> Development of pancreatic cancer in spontaneous murine models is associated with enrichment of specific strains of gut and intratumoral bacteria that induce a tolerogenic immunosuppressive microenvironment favoring cancer progression and resistance to immunotherapies. Ablation of the microbiome with antibiotics reshapes the tumor microenvironment, inducing T-cell activation, improving immune surveillance, and increasing sensitivity to immunotherapy in established tumors. Cancer Discov; 8(4); 386-8...
April 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29599908/regulatory-b-cells-induced-by-pancreatic-cancer-cell-derived-interleukin-18-promote-immune-tolerance-via-the-pd-1-pd-l1-pathway
#11
Yan Zhao, Ming Shen, Yecheng Feng, Ruizhi He, Xiaodong Xu, Yu Xie, Xiuhui Shi, Min Zhou, Shutao Pan, Min Wang, Xingjun Guo, Renyi Qin
Dysregulation of regulatory B cells (Bregs), a type of immunosuppressive lymphocyte, are associated with development of autoimmune diseases and cancers. Bregs produce immune tolerance-inducing cell surface molecules and tolerogenic cytokines (interleukin [IL]-10 and transforming growth factor-beta). We previously showed that levels of the inflammatory cytokine IL-18 were increased in patients with pancreatic cancer. In the present study study, we found that pancreatic cancer cell-derived IL-18 increases Breg-induced immunosuppression...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29588348/intratumoral-cpg-b-promotes-anti-tumoral-neutrophil-cdc-and-t-cell-cooperation-without-reprograming-tolerogenic-pdc
#12
Marion Humbert, Leslie Guery, Dale Brighouse, Sylvain Lemeille, Stephanie Hugues
Cancer immunotherapies utilize distinct mechanisms to harness the power of the immune system to eradicate cancer cells. Therapeutic vaccines, aimed at inducing active immune responses against an existing cancer, are highly dependent on the immunological microenvironment, where many immune cell types display high levels of plasticity and, depending on the context, promote very different immunological outcomes. Among them, plasmacytoid dendritic cells (pDC), known to be highly immunogenic upon inflammation, are maintained in a tolerogenic state by the tumor microenvironment...
March 27, 2018: Cancer Research
https://www.readbyqxmd.com/read/29588277/tolerogenic-properties-of-fc-portion-of-igg-and-its-relevance-to-the-treatment-and-management-of-hemophilia
#13
Richard S Blumberg, David Lillicrap
Hemophilia, or inherited genetic deficiencies in coagulation factors result in uncontrolled bleeding requiring replacement therapy with recombinant proteins given preventively or on-demand. However, a major problem with these approaches is the potential for development of immune responses to the administered proteins due to the underlying genetic deficiency of the factor(s) throughout life. As such, there is great interest in developing strategies that avoid immunogenicity and induce immune tolerance. Recently, recombinant Factor VIII and Factor IX fused to the Fc domain of IgG have been developed as therapeutic agents for hemophilia A and B, respectively...
March 27, 2018: Blood
https://www.readbyqxmd.com/read/29578531/autophagy-in-dendritic-cells
#14
REVIEW
Ghita Ghislat, Toby Lawrence
Autophagy and immunity share the property of being auto-protective for the organism. Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. Perturbations in autophagy are associated with inflammation and cancer development. Emerging studies have characterized the molecular details regarding how autophagy is controlled by immune cells. Among these, dendritic cells (DCs) are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and cancer...
March 26, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29576315/liver-induced-transgene-tolerance-with-aav-vectors
#15
REVIEW
Geoffrey D Keeler, David M Markusic, Brad E Hoffman
Immune tolerance is a vital component of immunity, as persistent activation of immune cells causes significant tissue damage and loss of tolerance leads to autoimmunity. Likewise, unwanted immune responses can occur in inherited disorders, such as hemophilia and Pompe disease, in which patients lack any expression of protein, during treatment with enzyme replacement therapy, or gene therapy. While the liver has long been known as being tolerogenic, it was only recently appreciated in the last decade that liver directed adeno-associated virus (AAV) gene therapy can induce systemic tolerance to a transgene...
December 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29572810/chloroquine-treated-dendritic-cells-require-stat1-signaling-for-their-tolerogenic-activity
#16
Rodolfo Thome, Amanda Pires Bonfanti, Javad Rasouli, Elisabeth Rose Mari, Guang-Xian Zhang, Abdolmohamad Rostami, Liana Verinaud
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are T cell-driven autoimmune diseases of the central nervous system (CNS) where interleukin (IL)-17-producing Th17 cells promote damage and are pathogenic. Conversely, tolerogenic dendritic cells (DCs) induce regulatory T (Treg) cells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the modulation of DCs by unknown mechanisms. Here we show that signal transducer and activator of transcription (STAT) 1 is necessary for CQ-induced tolerogenic DCs (tolDCs) to efficiently suppress EAE...
March 23, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29567829/the-pancreatic-cancer-microbiome-promotes-oncogenesis-by-induction-of-innate-and-adaptive-immune-suppression
#17
Smruti Pushalkar, Mautin Hundeyin, Donnele Daley, Constantinos P Zambirinis, Emma Kurz, Ankita Mishra, Navyatha Mohan, Berk Aykut, Mykhaylo Usyk, Luisana E Torres, Gregor Werba, Kevin Zhang, Yuqi Guo, Qianhao Li, Neha Akkad, Sarah Lall, Benjamin Wadowski, Johana Gutierrez, Juan Andres Kochen Rossi, Jeremy W Herzog, Brian Diskin, Alejandro Torres-Hernandez, Josh Leinwand, Wei Wang, Pardeep S Taunk, Shivraj Savadkar, Malvin Janal, Anjana Saxena, Xin Li, Deirdre Cohen, R Balfour Sartor, Deepak Saxena, George Miller
We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4+ T cells and CD8+ T-cell activation...
March 22, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29564186/immunomodulation-in-hepatocellular-cancer
#18
REVIEW
Sunyoung Lee, Matthew Loecher, Renuka Iyer
Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the United States in relation to mortality. HCC relies on a complex immunosuppressive network to modify the host immune system and evade destruction. Intrinsic to the liver's function and anatomy, native hepatic and immune cells produce many inhibitory cytokines that promote tolerogenicity and limit immune response. Since the introduction of sorafenib in 2008, no treatment has been able to demonstrate improved survival in patients with advanced HCC post disease progression treated with sorafenib...
February 2018: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29563912/lipid-based-particles-versatile-delivery-systems-for-mucosal-vaccination-against-infection
#19
REVIEW
Blaise Corthésy, Gilles Bioley
Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29557913/extracorporeal-photopheresis-for-bronchiolitis-obliterans-syndrome-after-lung-transplantation
#20
Ramsey Hachem, Paul Corris
BACKGROUND: Lung transplantation is a therapeutic option for select patients with end-stage lung disease. However, successful lung transplantation is hampered by chronic lung allograft dysfunction (CLAD), in particular bronchiolitis obliterans syndrome (BOS). Although there is no approved or standard treatment for BOS, which may have several distinct phenotypes, extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment...
March 19, 2018: Transplantation
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