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Immunology and Cell Biology

Ahmad Kotb, Antonina Klippert, Maria Daskalaki, Ulrike Sauermann, Christiane Stahl-Hennig, Berit Neumann
Granzyme B-expressing (GrB(+)) B cells are thought to contribute to immune dysfunctions in HIV patients, but so far their exact role is unknown. This report demonstrates for the first time the existence of GrB(+) B cells in SIV-infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, we found significantly higher frequencies of these cells in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones. These frequencies correlated with plasma viral load and inversely with absolute CD4 T-cell counts...
October 25, 2016: Immunology and Cell Biology
Andreas Schlitzer, Joachim L Schultze
Tissue macrophages of fetal and adult origin have pivotal roles in tissue homeostasis and organ inflammation. Recently several functional and transcriptomic studies have revealed their unique module-like transcriptomic organization leading to enormous tissue-dependent functional plasticity. In this review, we discuss the development, tissue adaption and function of resident murine and human macrophages. Finally, we discuss our limited knowledge on human tissue macrophages and provide our opinion on their relevance during disease and for clinical application...
October 18, 2016: Immunology and Cell Biology
Mubing Duan, Margaret L Hibbs, Weisan Chen
The lung myeloid cell microenvironment comprises airway, alveolar and interstitial macrophages, peripheral blood recruited lung monocytes as well as residential and migratory dendritic cell subsets. Findings from fate mapping, parabiosis, transcriptome and epigenome profiling studies now indicate that tissue macrophage and monocyte subsets possess specialized functions which differentially impact homoeostatic tolerance, pathogen detection and pathogen killing. In the lungs, residential alveolar macrophages are catabolic and immunosuppressive in contrast to the classically pro-inflammatory repertoire of lung monocytes and monocyte-derived dendritic cells recruited during acute inflammation...
October 18, 2016: Immunology and Cell Biology
Maja Milanovic, Nicole Heise, Nilushi S De Silva, Michael M Anderson, Kathryn Silva, Amanda Carette, Fabiano Orelli, Govind Bhagat, Ulf Klein
Signaling through the canonical nuclear factor-κB (NF-κB) pathway is critical for the generation and maintenance of mature B cells and for antigen-dependent B-cell activation. c-REL (rel) and RELA (rela) are the downstream transcriptional activators of the canonical NF-κB pathway. Studies of B cells derived from constitutional rel knockout mice and chimeric mice repopulated with rela(-/-) fetal liver cells provided evidence that the subunits can have distinct roles during B-cell development. However, the B cell-intrinsic functions of c-REL and RELA during B-cell generation and antigen-dependent B-cell activation have not been determined in vivo...
October 18, 2016: Immunology and Cell Biology
Bruce D Wines, May L Yap, Maree S Powell, Peck-Szee Tan, K Kerry Ko, Eva Orlowski, P Mark Hogarth
The interleukin-23 (IL-23) pathway, T helper 17 (Th17) cells and γδ T cells, which respond to IL-23, have major pro-inflammatory roles. We have used unique IL-23 receptor (IL-23R) subunit-specific monoclonal antibodies, X67 and X68, and IL-12 receptor beta-1 subunit (IL-12Rβ1) expression levels to evaluate the IL-23R complex on CD4 αβ TCR Th17 cells and on γδ T cells. Both IL-23R and IL-12Rβ1 subunits constitute the functional IL-23R. Expression of the IL-23R subunit by cultured Th17 cells was heterogeneous...
October 18, 2016: Immunology and Cell Biology
Kevin V Chow, Robyn M Sutherland, Yifan Zhan, Andrew M Lew
Dendritic cells (DCs) are professional antigen presenting cells that consist of functionally and phenotypically heterogeneous populations. Monocyte derived dendritic cells (moDCs) are a DC subset that have been attracting increasing interest due to their potent influence on adaptive immune function and their rapid accumulation upon an inflammatory stimulus. Whilst early studies on moDCs mainly addressed infection, their emergence and function in other settings such as autoimmunity and allogeneic organ transplantation are now being increasingly appreciated...
October 17, 2016: Immunology and Cell Biology
Jimena Tosello Boari, Eva V Acosta Rodriguez
No abstract text is available yet for this article.
October 11, 2016: Immunology and Cell Biology
Tatiana Jofra, Roberta Di Fonte, Tarun Edgar Hutchinson, Farhad Dastmalchi, Giuseppe Galvani, Manuela Battaglia, Shahram Salek-Ardakani, Georgia Fousteri
PTPN22 (protein tyrosine phosphatase non receptor 22) encodes a tyrosine phosphatase that functions as a key regulator of immune homeostasis. In particular, PTPN22 inhibits T-cell receptor signaling and selectively promotes type I interferon responses in myeloid cells. To date, there is little information on the CD8 T-cell-intrinsic role of PTPN22 in response to a viral pathogen. We unexpectedly found that PTPN22-deficient virus-specific CD8 T cells failed to accumulate in wild-type hosts after lymphocytic choriomeningitis virus infection...
October 11, 2016: Immunology and Cell Biology
Pawan K Gupta, Sarah R Wagner, Qiang Wu, Rebecca A Shilling
γδ T cells producing interleukin-17A (γδT17) are thought to develop spontaneously in the thymus and to be maintained in the periphery. Previous studies suggested a role for T-helper 17 (Th17) cells in the maintenance of γδT17 via the expression of transforming growth factor-β1 (TGFβ1). However, we have previously found that Th17 cells were not required for expansion of γδT17 cells after lung transplant in a mouse model. Using mice deficient in signal transducer and activator of transcription 3 (STAT3) in CD4(+) T cells, which are unable to develop Th17 cells, we investigated the requirement for Th17 cells and TGFβ1 to maintain γδT17 cells in the lung and lymphoid tissues...
October 11, 2016: Immunology and Cell Biology
Yvonne Zeissig, Britt-Sabina Petersen, Andre Franke, Richard S Blumberg, Sebastian Zeissig
The study of rare phenotypes has a long history in the description of autoimmune disorders. First Mendelian syndromes of idiopathic tissue destruction were defined more than 100 years ago and were later revealed to result from immune-mediated reactivity against self. In the past two decades, continuous advances in sequencing technology and particularly the advent of next-generation sequencing have allowed to define the genetic basis of an ever-growing number of Mendelian forms of autoimmunity. This has provided unique insight into the molecular pathways that govern immunological homeostasis and that are indispensable for the prevention of self-reactive immune-mediated tissue damage and 'horror autotoxicus'...
October 11, 2016: Immunology and Cell Biology
Jenny Freitag, Luciana Berod, Thomas Kamradt, Tim Sparwasser
A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability and chronic pain, but also lead to considerable socio-economic costs. Given that the current treatment options are not curative, have substantial side effects and a high percentage of non-responders, innovative options to the existing therapeutic armament against autoimmune diseases are urgently required. Accumulating evidence suggests that changes in the metabolism of immune cells are associated with, and contribute to the pathogenesis of autoimmunity...
October 11, 2016: Immunology and Cell Biology
Anthony L DeFranco
Antibodies are involved in the pathogenesis of many autoimmune diseases. Although the mechanisms underlying the antibody response to infection or vaccination are reasonably well understood, we still have a poor understanding of the nature of autoimmune antibody responses. The most well studied are the anti-nuclear antibody responses characteristic of systemic lupus erythematosus and studies over the past decade or so have demonstrated a critical role for signaling by TLR7 and/or TLR9 in B cells to promote these responses...
October 11, 2016: Immunology and Cell Biology
Y Gallais, N Szely, F-X Legrand, A Leroy, M Pallardy, I Turbica
Patients treated with therapeutic biological products (BP) frequently develop anti-drug antibodies (ADA) with potential neutralizing capacities leading to loss of clinical response, or serious side effects. BP aggregates have been suggested to promote immunogenicity thus enhancing ADA production. Dendritic cells (DC) are key effectors in T-cell and B-cell fates and the subsequent generation of immunogenicity. The objective of this work was to determine if BP aggregates can participate to DC maturation and T-cell activation...
October 7, 2016: Immunology and Cell Biology
Sachin Sharma, Thomas Kaufmann, Subhrajit Biswas
The routes leading to programmed cell death are as tightly regulated as those of cellular growth and proliferation, and a finely synchronized balance between the life and death of cells ensures proper organ size and function. Inhibitors of apoptosis (IAPs) proteins were initially characterized by their ability to directly bind and inhibit apoptotic caspases. However, recent studies have clarified that IAPs are much more functionally versatile, modulating a vast range of signaling pathways that have an impact on antimicrobial responses, tumorigenesis, metastasis and cellular migration...
October 7, 2016: Immunology and Cell Biology
You-Qiang Jian, Jian Ye, Hui Qi, Chun-Yan Deng, Shao-Ping Deng, Fu-Rong Li
Donor-reactive memory T (Tm)cells mediate accelerated rejection, which is known as a barrier to the survival of transplanted organs. Selective interference with the anti-CD45RB monoclonal antibody (α-CD45RB) reliably induces donor-specific tolerance. In this study, pre-sensitization to female C57BL/6 mice with the skin of female BLAB/c mice generated a large number of Tm cells and resulted in rapid rejection of the secondly transplanted allografts. α-CD45RB did induce the tolerance to skin allograft primarily transplanted but failed to induce tolerance in the pre-sensitized mice...
October 4, 2016: Immunology and Cell Biology
Lisa Zondler, Marisa S Feiler, Axel Freischmidt, Wolfgang P Ruf, Albert C Ludolph, Karin M Danzer, Jochen H Weishaupt
Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease affecting predominantly motor neurons in the spinal cord and motor cortex. Neurodegeneration in ALS is accompanied by a well-characterized neuroinflammatory reaction within the central nervous system and, as described more recently, cells of the peripheral immune system. Particularly monocytes have been implicated in ALS pathogenesis. Exosomes are membrane-enclosed vesicles secreted by various cell types with a diameter of 50-150 nm...
October 4, 2016: Immunology and Cell Biology
Hem R Gurung, Meghan M Carr, Daniel J J Carr
Herpes simplex virus-1 (HSV-1) infection of the cornea induces vascular endothelial growth factor A (VEGF-A)-dependent lymphangiogenesis. However, the extent to which HSV-1-induced corneal lymphangiogenesis impacts the adaptive immune response has not been characterized. Here, we used floxed VEGF-A mice to study the importance of newly created corneal lymphatic vessels in the host adaptive immune response to infection. Whereas the mice infected with the parental virus (strain SC16) exhibited robust corneal lymphangiogenesis, mice that received the recombinant virus (SC16 ICP0-Cre) that expresses Cre recombinase under the control of infected cell protein 0 (ICP0), an HSV-1 immediate-early gene, showed a significant reduction in lymphangiogenesis...
October 4, 2016: Immunology and Cell Biology
Thi Ho Nguyen, Nicola L Bird, Emma J Grant, John J Miles, Paul G Thomas, Tom C Kotsimbos, Nicole A Mifsud, Katherine Kedzierska
Epstein-Barr virus (EBV) is one of the most common viruses in humans, capable of causing life-threatening infections and cancers in immunocompromised individuals. Although CD8(+) T cells provide key protection against EBV, the persistence and dynamics of specific T-cell receptor (TCR) clones during immunosuppression in transplant patients is largely unknown. For the first time, we used a novel single-cell TCRαβ multiplex-nested reverse transcriptase PCR to dissect TCRαβ clonal diversity within GLCTLVAML (GLC)-specific CD8(+) T cells in healthy individuals and immunocompromised lung transplant recipients...
October 4, 2016: Immunology and Cell Biology
Delgertsetseg Chuluundorj, Scott A Harding, David Abernethy, Anne Camille La Flamme
Multiple sclerosis (MS) is an immune-mediated disease of the CNS, and monocytes contribute to MS-associated neuroinflammation. While classically-activated monocytes promote inflammation, type II-activated monocytes improve the course of MS. This study investigated type II activation of monocytes and their two main subsets, namely CD14(+) (CD14(++)CD16(-)subset) and CD16(+) monocytes (CD14(+)CD16(+)subset), by glatiramer acetate (GA) or intravenous immunoglobulin (IVIG)-associated immune complexes (IC), both of which are known MS treatments...
October 3, 2016: Immunology and Cell Biology
Donghee Kim, Song Mi Lee, Hee-Sook Jun
Type 1 diabetes results from autoimmune-mediated pancreatic beta cell destruction and TGF-β is known to play a preventive role in type 1 diabetes in non-obese diabetic (NOD) mice. In this study, we investigated the role of Smad4, a key molecule for Smad-dependent TGF-β signaling, in T cells of NOD mice in the pathogenesis of autoimmune diabetes. We generated T cell-specific Smad4 knockout (Smad4 tKO) NOD mice and assessed the pathological and immunological changes. Smad4 tKO showed earlier onset and increased incidence of diabetes than wild-type (WT) NOD mice...
September 30, 2016: Immunology and Cell Biology
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