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https://www.readbyqxmd.com/read/28733878/role-of-tgf-%C3%AE-in-self-peptide-regulation-of-autoimmunity
#1
REVIEW
Bhagirath Singh, Michael D Krawetz, Rachel M De Lima, Rinee Mukherjee, Pratibha Chaturvedi, Edwin Lee-Chan, Edward H Leiter, Kelly L Summers
Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins...
July 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28723951/cd8-t-cells-provide-immune-protection-against-murine-disseminated-endotheliotropic-orientia-tsutsugamushi-infection
#2
Guang Xu, Nicole L Mendell, Yuejin Liang, Thomas R Shelite, Yenny Goez-Rivillas, Lynn Soong, Donald H Bouyer, David H Walker
Scrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treatment, the disease can cause severe multiorgan failure with a case fatality rate of 7-15%. The current gaps in knowledge of immunity include the unknown mechanisms of host immunity to O. tsutsugamushi. Using an intravenous (i...
July 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28720143/mhc-class-ii-expression-and-potential-antigen-presenting-cells-in-the-retina-during-experimental-autoimmune-uveitis
#3
Deborah A Lipski, Rémi Dewispelaere, Vincent Foucart, Laure E Caspers, Matthieu Defrance, Catherine Bruyns, François Willermain
BACKGROUND: Controversy exists regarding which cell types are responsible for autoantigen presentation in the retina during experimental autoimmune uveitis (EAU) development. In this study, we aimed to identify and characterize the retinal resident and infiltrating cells susceptible to express major histocompatibility complex (MHC) class II during EAU. METHODS: EAU was induced in C57BL/6 mice by adoptive transfer of autoreactive lymphocytes from IRBP1-20-immunized animals...
July 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28719024/the-immunoproteasome-an-old-player-with-a-novel-and-emerging-role-in-alloimmunity
#4
S K Eskandari, M A J Seelen, G Lin, J R Azzi
Modern treatment strategies for the maintenance of allograft acceptance frequently target ubiquitously-expressed pathways, leading to significant side-effects and poor long-term allograft outcomes. Constitutive proteasome inhibitors, which have recently been introduced for the treatment of antibody-mediated rejection, target the ubiquitously-expressed proteasome. To limit off-target effects and serious mechanism-based toxicity, however, these inhibitors are administered intermittently and suboptimally. Immunoproteasomes, which are an inducible subset of proteasomes enriched in immune cells, replace constitutive proteasomes after cell exposure to proinflammatory cytokines such as interferon-γ...
July 18, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#5
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28714192/secreted-tumor-antigens-immune-biomarkers-for-diagnosis-and-therapy
#6
REVIEW
Els N Meeusen, Elgene Lim, Suresh Mathivanan
With the advent of immunotherapies for cancer, there is growing interest in the identification of tumor antigens. Tumor antigens are self-molecules altered through genetic mutations (neoantigens), protein truncation, protein misfolding or abnormal post translational modifications. To induce an immune response, tumor antigens need to be secreted into the tumor environment and presented to the immune system in the draining lymph nodes, resulting in the generation of tumor-specific effector cells and antibodies...
July 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28708252/redundant-and-regulatory-roles-for-tlrs-in-leishmania-infection
#7
REVIEW
Prashant Chauhan, Divanshu Shukla, Debprasad Chattopadhyay, Bhaskar Saha
Toll-like receptors (TLRs) are germ-line encoded, non-clonal innate immune receptors, which are often the first receptors to recognize the molecular patterns on pathogens. Therefore, the immune response initiated by TLRs does have far-reaching consequences on the outcome of an infection. As soon as the cell surface TLRs and other receptors recognize a pathogen, the pathogen is phagocytosed. Inclusion of TLRs in the phagosome results in quicker phagosomal maturation and stronger adaptive immune response, as TLRs influence costimulatory molecules expression and determinant selection by MHC class-II and by MHC class-I for cross-presentation...
July 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28700752/role-of-a-novel-immune-modulating-ddr2-expressing-population-in-silica-induced-pulmonary-fibrosis
#8
Lindsay T McDonald, Sara D Johnson, Dayvia L Russell, M Rita I Young, Amanda C LaRue
Micro-injuries associated with chronic inhaled particle exposures are linked with activation of the immune response and are thought to contribute to progression of fibrotic disease. In the pulmonary environment, we have previously demonstrated a heterogeneous population of circulating fibroblast precursors (CFPs), which are defined by expression of the pan-leukocyte marker CD45 and the collagen receptor, discoidin domain receptor-2 (DDR2). This population is derived from the hematopoietic stem cell, expresses collagen, and has a fibroblastic morphology in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28699110/immune-selection-during-tumor-checkpoint-inhibition-therapy-paves-way-for-nk-cell-missing-self-recognition
#9
REVIEW
Karl-Johan Malmberg, Ebba Sohlberg, Jodie P Goodridge, Hans-Gustaf Ljunggren
The ability of NK cells to specifically recognize cells lacking expression of self-MHC class I molecules was discovered over 30 years ago. It provided the foundation for the "missing self" hypothesis. Research in the two past decades has contributed to a detailed understanding of the molecular mechanisms that determine the specificity and strength of NK cell-mediated "missing self" responses to tumor cells. However, in light of the recent remarkable breakthroughs in clinical cancer immunotherapy, the cytolytic potential of NK cells still remains largely untapped in clinical settings...
July 11, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28695294/the-role-of-mhc-genes-in-contagious-cancer-the-story-of-tasmanian-devils
#10
REVIEW
Alison Caldwell, Hannah V Siddle
The Tasmanian devil, a marsupial species endemic to the island of Tasmania, harbours two contagious cancers, Devil Facial Tumour 1 (DFT1) and Devil Facial Tumour 2 (DFT2). These cancers pass between individuals in the population via the direct transfer of tumour cells, resulting in the growth of large tumours around the face and neck of affected animals. While these cancers are rare, a contagious cancer also exists in dogs and five contagious cancers circulate in bivalves. The ability of tumour cells to emerge and transmit in mammals is surprising as these cells are an allograft and should be rejected due to incompatibility between Major Histocompatibility Complex (MHC) genes...
July 11, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28695288/introduction-mhc-kir-and-governance-of-specificity
#11
REVIEW
Adrian Kelly, John Trowsdale
The MHC controls specificity, to ensure that appropriate immune responses are mounted to invading pathogens whilst maintaining tolerance to the host. It encodes molecules that act as sentinels, providing a snapshot of the health of the interior and exterior of the cell for immune surveillance. To maintain the ability to respond appropriately to any disease requires a delicate balance of expression and function, and many subtleties of the system have been described at the gene, individual and population level...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28694293/the-trophic-life-cycle-stage-of-the-opportunistic-fungal-pathogen-pneumocystis-murina-hinders-the-ability-of-dendritic-cells-to-stimulate-cd4-t-cell-responses
#12
Heather M Evans, Andrew Simpson, Shu Shen, Arnold J Stromberg, Carol L Pickett, Beth A Garvy
The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple PAMPs, including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding transcription factors...
July 10, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28688841/how-mr1-presents-a-pathogen-metabolic-signature-to-mucosal-associated-invariant-t-mait-cells
#13
REVIEW
Hamish E G McWilliam, Jose A Villadangos
Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes restricted by the antigen (Ag)-presenting molecule MHC class I (MHC I)-related protein 1 (MR1). The Ags presented by MR1 are vitamin B-related Ags (VitBAgs), 'building-block' metabolites of riboflavin that are synthesized by a range of microbes. MR1 presentation is thus a unique mechanism for the immune detection of a pathogen metabolic signature. While the full picture of how MR1 accomplishes this remains incomplete, recent data show that, unlike other MHC molecules, MR1 operates by a presentation-on-demand mechanism...
July 5, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28680379/diclofenac-inhibits-27-hydroxycholesterol-induced-differentiation-of-monocytic-cells-into-mature-dendritic-cells
#14
Yonghae Son, Bo-Young Kim, Young Chul Park, Koanhoi Kim
We investigated whether diclofenac could influence the development of antigen-presenting cells in an oxygenated cholesterol-rich environment by determining its effects on the 27-hydroxycholesterol (27OHChol)-induced differentiation of monocytic cells into mature dendritic cells (mDCs). Treatment of human THP-1 monocytic cells with diclofenac antagonized the effects of 27OHChol by attenuating dendrite formation and cell attachment and promoting endocytic function. Diclofenac inhibited the transcription and surface expression of the mDC markers of CD80, CD83, and CD88, and reduced the 27OHChol-induced elevation of surface levels of MHC class I and II molecules to the basal levels in a dose-dependent manner...
June 2017: Immune Network
https://www.readbyqxmd.com/read/28676677/hla-e-presents-glycopeptides-from-the-mycobacterium-tuberculosis-protein-mpt32-to-human-cd8-t-cells
#15
Melanie J Harriff, Lisa M Wolfe, Gwendolyn Swarbrick, Megan Null, Meghan E Cansler, Elizabeth T Canfield, Todd Vogt, Katelynne Gardner Toren, Wei Li, Mary Jackson, Deborah A Lewinsohn, Karen M Dobos, David M Lewinsohn
Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. Both classically and non-classically restricted cytotoxic CD8(+) T cells are important to the control of Mtb infection. We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8(+) T cells. In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8(+) T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673339/human-limbal-fibroblast-like-stem-cells-induce-immune-tolerance-in-autoreactive-t-lymphocytes-from-female-patients-with-hashimoto-s-thyroiditis
#16
Antonina Coppola, Laura Tomasello, Maria Pitrone, Salvatore Cillino, Pierina Richiusa, Giuseppe Pizzolanti, Carla Giordano
BACKGROUND: Due to their "natural immune privilege" and immunoregulatory properties human fibroblast-like limbal stem cells (f-LSCs) have acquired great interest as a potential tool for achieving immunotolerance. Hashimoto's thyroiditis (HT) is the most common thyroid autoimmune disease and cause of hypothyroidism. To date, conventional hormone replacement therapy and unspecific immunosuppressive regimens cannot provide a definitive cure for HT subjects. We explored the immunosuppressant potential of human f-LSCs on circulating lymphomonocytes (PBMCs) collected from healthy donors and female HT patients...
July 3, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28663435/critical-role-for-sec22b-dependent-antigen-cross-presentation-in-antitumor-immunity
#17
Andrés Alloatti, Derek C Rookhuizen, Leonel Joannas, Jean-Marie Carpier, Salvador Iborra, Joao G Magalhaes, Nader Yatim, Patrycja Kozik, David Sancho, Matthew L Albert, Sebastian Amigorena
CD8(+) T cells mediate antigen-specific immune responses that can induce rejection of solid tumors. In this process, dendritic cells (DCs) are thought to take up tumor antigens, which are processed into peptides and loaded onto MHC-I molecules, a process called "cross-presentation." Neither the actual contribution of cross-presentation to antitumor immune responses nor the intracellular pathways involved in vivo are clearly established because of the lack of experimental tools to manipulate this process. To develop such tools, we generated mice bearing a conditional DC-specific mutation in the sec22b gene, a critical regulator of endoplasmic reticulum-phagosome traffic required for cross-presentation...
June 29, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28652982/reactivity-of-commercially-available-monoclonal-antibodies-to-human-cd-antigens-with-peripheral-blood-leucocytes-of-dromedary-camels-camelus-dromedarius
#18
Jamal Hussen, Turke Shawaf, Abdulkareem Imran Al-Herz, Hussain R Alturaifi, Ahmed M Alluwaimi
Monoclonal antibodies (mAbs) to cell surface molecules have been proven as a key tool for phenotypic and functional characterization of the cellular immune response. One of the major difficulties in studying camel cellular immunity consists in the lack of mAbs that dtect their leukocyte differentiation antigens. In the present study two-parameter flow cytometry was used to screen existing commercially available mAbs to human leukocyte antigens and major histocompatibility molecules (MHC) for their reactivity with camel leukocytes...
2017: Open veterinary journal
https://www.readbyqxmd.com/read/28649242/an-approach-for-a-synthetic-ctl-vaccine-design-against-zika-flavivirus-using-class-i-and-class-ii-epitopes-identified-by-computer-modeling
#19
Edecio Cunha-Neto, Daniela S Rosa, Paul E Harris, Tim Olson, Alex Morrow, Serban Ciotlos, Charles V Herst, Reid Martin Rubsamen
The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#20
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
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