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Immunology

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https://www.readbyqxmd.com/read/28718505/immunogenomic-approaches-to-understand-the-function-of-immune-disease-variants
#1
REVIEW
Dafni Anna Glinos, Blagoje Soskic, Gosia Trynka
Mapping hundreds of genetic variants through genome wide association studies provided an opportunity to gain insights into the pathobiology of immune mediated diseases. However, since most of the disease variants fall outside the gene coding sequences, thereby implicating gene expression regulation as the causal mechanism, the functional interpretation of the exact role of the associated variants remains to be determined. Despite these challenges, integration of disease associated variants with large scale genomic maps of cell type specific gene regulation both at chromatin and transcript levels deliver examples of functionally prioritised causal variants and genes...
July 17, 2017: Immunology
https://www.readbyqxmd.com/read/28718500/neurofilament-light-as-an-immune-target-for-pathogenic-antibodies
#2
Fabiola Puentes, Baukje J van der Star, Stephanie D Boomkamp, Markus Kipp, Louis Boon, Isabel Bosca, Joel Raffel, Sharmilee Gnanapavan, Paul van der Valk, Jodie Stephenson, Susan C Barnett, David Baker, Sandra Amor
Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunisation with neuronal antigens such as neurofilament light NF-L, a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, while antibodies to NF-L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to NF-L contribute to neurodegeneration and neurological disease...
July 17, 2017: Immunology
https://www.readbyqxmd.com/read/28707699/predict-disease-progression-from-t-cell-phenotypes-in-northern-pig-tailed-macaques-macaca-leonina-during-sivmac239-infection
#3
Ming-Xu Zhang, Hong-Yi Zheng, Jin Jiang, Jia-Hao Song, Min Chen, Yu Xiao, Xiao-Dong Lian, Tian-Zhang Song, Ren-Rong Tian, Wei Pang, Yong-Tang Zheng
Macaca leonina (northern pig-tailed macaques, NPMs) have variable disease progression during SIVmac239 infection. In the present study, we analyzed, for the first time, the correlations between T cell phenotypes and disease progression in NPMs during SIVmac239 infection. In comparison to normal progressors (NPs), slow progressors (SPs) had lower chronic T cell activation and exhaustion levels. In addition, SPs showed higher peripheral CD4+ T cell count, CD4/CD8 ratio and lower plasma viral load than NPs. CD4+ T cell count and CD4/CD8 ratio decreased more sharply in NPs than in SPs...
July 14, 2017: Immunology
https://www.readbyqxmd.com/read/28704588/here-there-and-everywhere-t-follicular-helper-cells-on-the-move
#4
REVIEW
Cindy S Ma, Tri Giang Phan
T follicular helper (Tfh) cells have the important function of providing B cell help for the induction of Ag-specific Ab production. As such it is important to determine the factors that regulate the development, differentiation and function of Tfh cells. This review highlights some of the recent advances in our understanding of Tfh cell migration, Tfh cell memory and the origins and fate of circulating Tfh (cTfh) cells in the blood that have been revealed from studies in humans and mice. This article is protected by copyright...
July 13, 2017: Immunology
https://www.readbyqxmd.com/read/28704576/psychosis-an-autoimmune-disease
#5
REVIEW
Adam Aj Al-Diwani, Thomas A Pollak, Sarosh R Irani, Belinda R Lennox
Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways...
July 13, 2017: Immunology
https://www.readbyqxmd.com/read/28703297/neither-eosinophils-nor-neutrophils-require-atg5-dependent-autophagy-for-extracellular-dna-trap-formation
#6
Nina Germic, Darko Stojkov, Kevin Oberson, Shida Yousefi, Hans-Uwe Simon
The importance of extracellular traps (ETs) in innate immunity is well established, but the molecular mechanisms responsible for their formation remain unclear and in scientific dispute. ETs have been defined as extracellular DNA scaffolds associated with the granule proteins of eosinophils or neutrophils. They are capable of killing bacteria extracellularly. Based mainly on results with phosphoinositide 3-kinase (PI3K) inhibitors such as 3-methyladenine (3-MA) and wortmannin which are commonly used to inhibit autophagy, several groups have reported that autophagy is required for neutrophil extracellular trap (NET) formation...
July 13, 2017: Immunology
https://www.readbyqxmd.com/read/28699278/regulatory-t-cells-in-skin
#7
REVIEW
Niwa Ali, Michael D Rosenblum
Foxp3+ CD4+ Regulatory T cells (Tregs) are a subset of immune cells that function to regulate tissue inflammation. Skin is one of the largest organs and is home to a large proportion of the body's Tregs. However, relative to other tissues (such as the spleen and gastrointestinal tract) the function of Tregs in skin is less well defined. Here, we review our understanding of how Tregs migrate to skin and the cellular and molecular pathways required for their maintenance in this tissue. In addition, we outline what is known about the specialized functions of Tregs in skin...
July 12, 2017: Immunology
https://www.readbyqxmd.com/read/28699226/ebv-provides-survival-factors-to-ebv-dlbcl-lines-and-modulates-cytokine-induced-specific-chemotaxis-in-ebv-dlbcl
#8
Liang Wu, Barbro Ehlin-Henriksson, Xiaoying Zhou, Hong Zhu, Ingemar Ernberg, Lorand L Kis, George Klein
Diffuse large B-cell lymphoma (DLBCL), the most common type of malignant lymphomas, account for 30% of adult non-Hodgkin lymphomas (NHLs). EBV-positive DLBCL of the elderly is a newly recognized subtype that accounts for 8% to 10% of DLBCL in Asian countries, but is less common in Western populations. Five DLBCL derived cell lines were employed to characterize patterns of EBV latent gene expression, as well as response to cytokines and chemotaxis. IL-4 and IL-21 modified LMP1-, EBNA1- and EBNA2-expression depending on cell phenotype and type of EBV latent program (type I, II or III)...
July 12, 2017: Immunology
https://www.readbyqxmd.com/read/28695629/caspase-11-non-canonical-inflammasome-a-critical-sensor-of-intracellular-lps-in-macrophage-mediated-inflammatory-responses
#9
REVIEW
Young-Su Yi
Inflammatory responses mediated by macrophages are part of the innate immune system, whose role is to protect against invading pathogens. Lipopolysaccharide (LPS) found in the outer membrane of Gram-negative bacteria stimulate an inflammatory response by macrophages. During the inflammatory response, extracellular LPS are recognized by Toll-like receptor 4 (TLR4), one of the pattern recognition receptors (PRRs) that activates inflammatory signaling pathways and leads to the production of inflammatory mediators...
July 10, 2017: Immunology
https://www.readbyqxmd.com/read/28685821/pd-1-pd-l1-inhibitors-in-haematological-malignancies-update-2017
#10
REVIEW
Tomas Jelinek, Jana Mihalyova, Michal Kascak, Juraj Duras, Roman Hajek
The introduction of PD-1/PD-L1 pathway inhibitors is an important landmark in solid oncology with unprecedented practice-changing activity in various types of solid tumours. Amongst haematological malignancies, PD-1/PD-L1 inhibitors have been successful, so far, only in the treatment of classical Hodgkin lymphoma, which typically exhibits an over-expression of PD-1 ligands (PD-L1, PD-L2) due to alterations in chromosome 9p24.1. Such positive outcomes led to the FDA approval of nivolumab use in relapsed Hodgkin lymphoma in 2016 as the first haematological indication...
July 6, 2017: Immunology
https://www.readbyqxmd.com/read/28685820/pi3k-akt-pathway-enhances-the-differentiation-of-il-27-induced-type-1-regulatory-t-cells
#11
Niken Adiba Nadya, Hiroyuki Tezuka, Toshiaki Ohteki, Satoshi Matsuda, Miyuki Azuma, Shigenori Nagai
Interleukin 27 (IL-27) has been identified as a potent cytokine in the differentiation of type 1 regulatory T (Tr1) cells through interactions with several key elements, including transcription factors such as aryl hydrocarbon receptor and IL-21. Autocrine production of IL-21 is known to be important for maintaining IL-10 expression by Tr1 cells. Although previous studies have shown that the PI3K-Akt axis contributes to the differentiation of helper T cell subsets, the role of the PI3K pathway on Tr1 cell differentiation remains to be elucidated...
July 6, 2017: Immunology
https://www.readbyqxmd.com/read/28672048/slfn2-mutation-induced-loss-of-t-cell-quiescence-leads-to-elevated-de-novo-sterol-synthesis
#12
Ibrahim Omar, Oren Rom, Michael Aviram, Leonor Cohen-Daniel, Abraham K Gebre, John S Parks, Michael Berger
Acquisition of a "quiescence program" by naïve T cells is important to provide a stress-free environment and resistance to apoptosis while preserving their responsiveness to activating stimuli. Therefore, the survival and proper function of naïve T cells depends on their ability to maintain quiescence. Recently we demonstrated that by preventing chronic unresolved endoplasmic reticulum (ER) stress, Schlafen2 (Slfn2) maintains a stress-free environment to conserve a pool of naïve T cells ready to respond to a microbial invasion...
July 3, 2017: Immunology
https://www.readbyqxmd.com/read/28670716/adoptive-transfer-of-murine-t-cells-expressing-a-chimeric-pd1-dap10-receptor-as-an-immunotherapy-for-lymphoma
#13
Adam Lynch, William Hawk, Emily Nylen, Sean Ober, Pierre Autin, Amorette Barber
Adoptive transfer of T cells is a promising cancer therapy and expression of chimeric antigen receptors can enhance tumor recognition and T cell effector functions. The PD1 receptor is a prospective target for a chimeric antigen receptor because PD1 ligands are expressed on many cancer types, including lymphoma. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 extracellular domain fused to the cytoplasmic domain of CD3 zeta. Additionally, chimeric antigen receptor therapies utilize various costimulatory domains to enhance efficacy...
July 3, 2017: Immunology
https://www.readbyqxmd.com/read/28670688/lack-of-ikaros-cripples-expression-of-foxo1-and-its-targets-in-naive-t-cells
#14
Parul Agnihotri, Nicholas M Robertson, Sarah E Umetsu, Ksenia Arakcheeva, Susan Winandy
Ikaros is a transcription factor that regulates lymphocyte development from the level of the hematopoietic stem cell. Lack of Ikaros reduces the ability of progenitor cells to commit to the T cell lineage, resulting in reduced numbers of early thymic T cell progenitors and mature T cells. Mature CD4 T cells that lack Ikaros have defects in proliferation, T helper cell differentiation, cytokine expression and the ability to become anergic. A role for Ikaros in the naïve T cell has not yet been identified. IL-7Rα and L-selectin are receptors important for ensuring survival and proper homing of naive T cells, respectively...
July 3, 2017: Immunology
https://www.readbyqxmd.com/read/28664991/artificial-human-antigen-presenting-cells-are-superior-to-dendritic-cells-at-inducing-cytotoxic-t-cell-responses
#15
Hua Li, Shengwen Shao, Jianshu Cai, Danielle Burner, Lingeng Lu, Qiuqiang Chen, Boris Minev, Wenxue Ma
Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes (CTLs) leads to the killing of cancer cells. A potential challenge for T-cell immunotherapy is that dendritic cells (DCs) are exposed to the MHC class I-peptide complex for an insufficient amount of time. To improve tumor antigen presentation to T cells and thereby initiate a more effective T cell response, we generated artificial antigen-presenting cells (aAPCs) by incubating human immature DCs (imDCs) with poly(lactic-co-glycolic) acid nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides, followed by the maturation with lipopolysaccharide (LPS)...
June 30, 2017: Immunology
https://www.readbyqxmd.com/read/28653395/parp14-limits-severity-of-allergic-skin-disease
#16
Purna Krishnamurthy, Sonia Da-Silva-Arnold, Matthew J Turner, Jeffrey B Travers, Mark H Kaplan
Poly-ADP ribose polymerase-14 (PARP14 or ARTD8) was initially identified as a transcriptional co-activator for Stat6, where the presence of IL-4 and activated Stat6 induces the enzymatic activity of PARP14 that promotes Th2 differentiation and allergic airway disease. To further our understanding of PARP14 in allergic disease, we studied the function of PARP14 in allergic inflammation of skin using mice that express constitutively active Stat6 in T cells (Stat6VT) and develop spontaneous inflammation of the skin...
June 27, 2017: Immunology
https://www.readbyqxmd.com/read/28646586/vaccine-candidate-discovery-for-the-next-generation-of-malaria-vaccines
#17
REVIEW
James Tuju, Gathoni Kamuyu, Linda M Murungi, Faith H A Osier
Although epidemiological observations, IgG passive transfer studies and experimental infections in humans all support the feasibility of developing highly effective malaria vaccines, the precise antigens that induce protective immunity remain uncertain. Here, we review the methodologies applied to vaccine candidate discovery for Plasmodium falciparum malaria from the pre- to post- genomic era. Probing of genomic and/or cDNA libraries with antibodies of defined specificities or functional activity predominated the former, while reverse vaccinology encompassing high throughput in silico analyses of genomic, transcriptomic or proteomic parasite datasets is the mainstay of the latter...
June 24, 2017: Immunology
https://www.readbyqxmd.com/read/28646573/interferon-%C3%AE-regulates-dendritic-cell-activation-and-migration-in-experimental-autoimmune-encephalomyelitis
#18
Leesa M Pennell, Eleanor N Fish
CD11c+ dendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon (IFN)-β treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β(+/+) and IFN-β(-/-) mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-β(-/-) mice exhibit earlier onset and more rapid progression of neurologic impairment compared with IFN-β(+/+) mice...
June 24, 2017: Immunology
https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#19
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28628194/signals-that-drive-t-follicular-helper-cell-formation
#20
REVIEW
Louise M C Webb, Michelle A Linterman
T follicular helper (TFH) cells are a distinct type of CD4+ T cell specialized in providing help to B cells during the germinal center (GC) reaction. As such, they are critical determinants of the quality of an antibody response following antigen challenge. Excessive production of TFH cells can result in autoimmunity whilst too few can result in inadequate protection from infection. Hence, their differentiation and maintenance must be tightly regulated to ensure appropriate, but limited, help to B cells. Unlike the majority of other CD4+ T cell subsets, TFH cell differentiation occurs in three phases defined by their anatomical location...
June 19, 2017: Immunology
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