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Immunological pathways

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https://www.readbyqxmd.com/read/28329310/immunologic-pathways-that-predict-mortality-in-hiv-infected-ugandans-initiating-art
#1
Sulggi Lee, Helen Byakwaga, Yap Boum, Tricia H Burdo, Kenneth C Williams, Michael M Lederman, Yong Huang, Russell P Tracy, Huyen Cao, Jessica E Haberer, Annet Kembabazi, David R Bangsberg, Jeffrey N Martin, Peter W Hunt
Plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated HIV disease in Ugandans compared to U.S.-based populations, Here, KT ratio, and T cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. Month 6 KT ratio (aHR=2.74), sCD14 (aHR=2.32), IL-6 (aHR=2.34), and D dimer (aHR=1.95) were associated with mortality occurring ≥6 months after ART initiation, KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings...
March 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28327619/il-36%C3%AE-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-via-nf%C3%AE%C2%BAb-activation-and-stat-transcription-factors
#2
A Harusato, H Abo, V L Ngo, S W Yi, K Mitsutake, S Osuka, J E Kohlmeier, J D Li, A T Gewirtz, A Nusrat, T L Denning
Regulatory and effector T helper (Th) cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4(+) T cells to potently inhibit Foxp3-expressing induced regulatory T cell (Treg) development, while concomitantly promoting the differentiation of Th9 cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28325629/towards-integrating-extracellular-matrix-and-immunological-pathways
#3
David F Boyd, Paul G Thomas
The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM...
March 18, 2017: Cytokine
https://www.readbyqxmd.com/read/28322382/regulation-of-raw-264-7-cell-mediated-immunity-by-polysaccharides-from-agaricus-blazei-murill-via-the-mapk-signal-transduction-pathway
#4
Feier Cheng, Xiaoyan Yan, Miaoqing Zhang, Mingchang Chang, Shaojun Yun, Junlong Meng, Jingyu Liu, Cui-Ping Feng
Agaricus blazei Murill (ABM) is a common anticancer folk remedy. Its active ingredients, i.e., polysaccharides, have been isolated and exhibit indirect tumor-suppressing activity via immunological activation. The effects of polysaccharides derived from A. blazei Murill (ABMP) on RAW 264.7 cells were examined by western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR). The effects of 500, 1000, and 2000 μg mL(-1) ABMP on the growth of RAW 264.7 cells were evaluated by measuring the OD490 value; the optimum concentration was found to be 1000 μg mL(-1)...
March 21, 2017: Food & Function
https://www.readbyqxmd.com/read/28317898/microrna-roles-in-signalling-during-lactation-an-insight-from-differential-expression-time-course-and-pathway-analyses-of-deep-sequence-data
#5
Duy N Do, Ran Li, Pier-Luc Dudemaine, Eveline M Ibeagha-Awemu
The study examined microRNA (miRNA) expression and regulatory patterns during an entire bovine lactation cycle. Total RNA from milk fat samples collected at the lactogenesis (LAC, day1 [D1] and D7), galactopoiesis (GAL, D30, D70, D130, D170 and D230) and involution (INV, D290 and when milk production dropped to 5 kg/day) stages from 9 cows was used for miRNA sequencing. A total of 475 known and 238 novel miRNAs were identified. Fifteen abundantly expressed miRNAs across lactation stages play regulatory roles in basic metabolic, cellular and immunological functions...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317886/systems-pharmacology-based-strategy-to-screen-new-adjuvant-for-hepatitis-b-vaccine-from-traditional-chinese-medicine-ophiocordyceps-sinensis
#6
Jingbo Wang, Rui Liu, Baoxiu Liu, Yan Yang, Jun Xie, Naishuo Zhu
Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28316970/dgk-%C3%AE-a-checkpoint-in-cancer-mediated-immuno-inhibition-and-target-for-immunotherapy
#7
Elfriede Noessner
Immunotherapy is moving to the forefront of cancer treatments owing to impressive durable responses achieved with checkpoint blockade antibodies and adoptive T-cell therapy. Still, improvements are necessary since, overall, only a small percentage of patients benefit from current therapies. Here, I summarize evidence that DGK-α may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytes in the tumor microenvironment. DGK-inhibitors can restore the antitumor function of tumor-suppressed adaptive and innate cytotoxic immunocytes...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28316598/t-cell-receptor-and-cytokine-signaling-can-function-at-different-stages-to-establish-and-maintain-transcriptional-memory-and-enable-t-helper-cell-differentiation
#8
REVIEW
Sarah L Bevington, Pierre Cauchy, David R Withers, Peter J L Lane, Peter N Cockerill
Experienced T cells exhibit immunological memory via a rapid recall response, responding to restimulation much faster than naïve T cells. The formation of immunological memory starts during an initial slow response, when naïve T cells become transformed to proliferating T blast cells, and inducible immune response genes are reprogrammed as active chromatin domains. We demonstrated that these active domains are supported by thousands of priming elements which cooperate with inducible transcriptional enhancers to enable efficient responses to stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28314518/the-interface-between-chronic-fatigue-syndrome-and-depression-a-psychobiological-and-neurophysiological-conundrum
#9
Derek Larkin, Colin R Martin
The chronic fatigue syndrome (CFS) remains a contentious and controversial presentation despite decades of systematic research from a variety of medical specialties and associated disciplines. Variously championed as a condition of immunological, neurological, neurophysiological, psychiatric or psychological origin, consensus on a cogent and evidenced-based pathway has yet to be achieved. Irrespective of the ambiguity regarding aetiology, what is incontrovertible is the experience of significant depression, which often accompanies this most distressing clinical presentation...
March 14, 2017: Neurophysiologie Clinique, Clinical Neurophysiology
https://www.readbyqxmd.com/read/28314211/the-role-of-kupffer-cells-in-hepatic-diseases
#10
REVIEW
Peizhi Li, Kun He, Jinzheng Li, Zuojin Liu, Jianping Gong
Kupffer cells (KCs) constitute 80-90% of the tissue macrophages present in the body. Essential to innate and adaptive immunity, KCs are responsible for the swift containment and clearance of exogenous particulates and immunoreactive materials which are perceived as foreign and harmful to the body. Similar to other macrophages, KCs also sense endogenous molecular signals that may result from perturbed homeostasis of the host. KCs have been implicated in host defense and the pathogenesis of various hepatic diseases, including endotoxin tolerance, liver transplantation, nonalcoholic fatty liver disease, and alcoholic liver disease...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28301259/novel-treatment-of-melanoma-combined-parasite-derived-peptide-gk-1-and-anti-programmed-death-ligand-1-therapy
#11
Jesus Vera-Aguilera, Armando Perez-Torres, Diego Beltran, Cynthia Villanueva-Ramos, Mitchell Wachtel, Eduardo Moreno-Aguilera, Carlos Vera-Aguilera, Gary Ventolini, Raul Martínez-Zaguilán, Souad R Sennoune
Recent successes in the development of new therapies for metastatic melanoma, such as mitogen-activated protein kinase pathway inhibitors, anticytotoxic T lymphocyte-associated antigen-4, and programmed cell death protein 1/programmed cell death ligand 1 (PD-L1) pathway-blocking antibodies, as well as combination strategies, all yielded promising results, changing the continually evolving landscape of therapeutic options for patients with melanoma. One promising new treatment modality is based on the use of immunomodulatory monoclonal antibodies that enhance the function of components of the antitumor immune response such as T cells or block immunologic checkpoints that restrain effective antitumor immunity...
March 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28299382/-immunological-mechanisms-of-allergen-specific-immunotherapy
#12
REVIEW
J-P Allam, N Novak
Allergen-specific immunotherapy is accompanied by multiple changes on the cellular and humoral level. A shift of Th2 immune responses towards immune responses of the Th1 type, which goes along with an increase of regulatory T cells and B cells, IL-10 as well as reduction of effector cells and eosinophils in the tissue, combined with lower IgE production in favor of higher IgG4 production, are regarded as key mechanisms of allergen-specific immunotherapy . A better understanding of immunologic pathways of specific immunotherapy would be essential for the improvement of this therapy as well as for the development of reliable biomarkers capable to monitor therapeutic responses as well as compliance of the patients...
March 15, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28296819/type-1-interferon-in-the-human-intestine-a-co-ordinator-of-the-immune-response-to-the-microbiota
#13
Edward M Giles, Andrew J Stagg
The human gut is in constant complex interaction with the external environment. Although much is understood about the composition and function of the microbiota, much remains to be learnt about the mechanisms by which these organisms interact with the immune system in health and disease. Type 1 interferon (T1IFN), a ubiquitous and pleiotropic family of cytokines, is a critical mediator of the response to viral, bacterial, and other antigens sampled in the intestine. Although inflammation is enhanced in mouse model of colitis when T1IFN signaling is lost, the action of T1IFN is context specific and can be pro- or anti-inflammatory...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28290609/senescence-of-mesenchymal-stem-cells-review
#14
Yi Li, Qiong Wu, Yujia Wang, Li Li, Hong Bu, Ji Bao
Mesenchymal stem cells (MSCs) have been used in cell-based therapy for various diseases, due to their immunomodulatory and inflammatory effects. However, the function of MSCs is known to decline with age, a process that is called senescence. To date, the process of MSC senescence remains unknown as in-depth understanding of the mechanisms involved in cellular senescence is lacking. First, senescent MSCs are so heterogeneous that not all of them express the same phenotypic markers. In addition, the genes and signaling pathways which regulate this process in MSCs are still unknown...
March 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28290451/development-of-sh2-probes-and-pull-down-assays-to-detect-pathogen-induced-site-specific-tyrosine-phosphorylation-of-the-tlr-adaptor-scimp
#15
Lin Luo, Samuel J Tong, Adam A Wall, Tatiana Khromykh, Matthew J Sweet, Jennifer L Stow
Protein tyrosine phosphorylation guides many molecular interactions for cellular functions. SCIMP is a transmembrane adaptor protein (TRAP) family member that mediates selective proinflammatory cytokine responses generated by pathogen-activated Toll-like receptor (TLR) pathways in macrophages. TLR activation triggers SCIMP phosphorylation and selective phosphorylation of distinct tyrosine residues on this adaptor offers the potential for regulating or biasing inflammatory responses. To analyze site-specific phosphorylation events, we developed three probes based on the SH2 domains of known SCIMP effectors, and used them for pull-downs from macrophage extracts...
March 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28289089/molecular-pathways-oncologic-pathways-and-their-role-in-t-cell-exclusion-and-immune-evasion-a-new-role-for-the-axl-receptor-tyrosine-kinase
#16
Todd A Aguilera, Amato J Giaccia
With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often non-existent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell inflamed tumors, and non-T-cell inflamed or T-cell excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development which result in T-cell exclusion...
March 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28288707/malt-lymphoma-genetic-abnormalities-immunological-stimulation-and-molecular-mechanism
#17
REVIEW
Ming-Qing Du
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) occurs at diverse anatomic sites and is closely associated with several distinct chronic inflammatory disorders. Both the acquired genetic abnormalities and active chronic immunological responses play a critical role in the development of MALT lymphoma, interestingly by dysregulating similar molecular mechanisms. The three translocations seen in MALT lymphoma, namely t(14;18)(q32;q21)/IGH-MALT1, t(1;14)(p22;q32)/BCL10-IGH, and t(11;18)(q21;q21)/BIRC3 (API2)-MALT1 are capable of activating both canonical and non-canonical NF-κB pathways...
March 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28287115/efficient-control-of-chronic-lcmv-infection-by-a-cd4-t-cell-epitope-based-heterologous-prime-boost-vaccination-in-a-murine-model
#18
Ran He, Xinxin Yang, Cheng Liu, Xiangyu Chen, Lin Wang, Minglu Xiao, Jianqiang Ye, Yuzhang Wu, Lilin Ye
CD4(+) T cells are essential for sustaining CD8(+) T cell responses during a chronic infection. The adoptive transfer of virus-specific CD4(+) T cells has been shown to efficiently rescue exhausted CD8(+) T cells. However, the question of whether endogenous virus-specific CD4(+) T cell responses can be enhanced by certain vaccination strategies and subsequently reinvigorate exhausted CD8(+) T cells remains unexplored. In this study, we developed a CD4(+) T cell epitope-based heterologous prime-boost immunization strategy and examined the efficacy of this strategy using a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection...
March 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28287114/regulation-of-inflammation-and-tumorigenesis-by-the-tipe-family-of-phospholipid-transfer-proteins
#19
REVIEW
Jason R Goldsmith, Youhai H Chen
The TIPE (tumor necrosis factor-α-induced protein 8-like) family are newly described regulators of immunity and tumorigenesis consisting of four highly homologous mammalian proteins: TNFAIP8 (tumor necrosis factor-α-induced protein 8), TIPE1 (TNFAIP8-like 1, or TNFAIP8L1), TIPE2 (TNFAIP8L2) and TIPE3 (TNFAIP8L3). They are the only known transfer proteins of the lipid secondary messengers PIP2 (phosphatidylinositol 4,5-bisphosphate) and PIP3 (phosphatidylinositol 3,4,5-trisphosphate). Cell-surface receptors, such as G-protein-coupled receptors and receptor tyrosine kinases, regulate inflammation and cancer via several signaling pathways, including the nuclear factor (NF)-κB and phosphoinositide-3 kinase (PI3K) pathways, the latter of which is upstream of both Akt and STAT3 activation...
March 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28287107/dying-cells-actively-regulate-adaptive-immune-responses
#20
REVIEW
Nader Yatim, Sean Cullen, Matthew L Albert
Dying cells have an important role in the initiation of CD8(+) T cell-mediated immunity. The cross-presentation of antigens derived from dying cells enables dendritic cells to present exogenous tissue-restricted or tumour-restricted proteins on MHC class I molecules. Importantly, this pathway has been implicated in multiple autoimmune diseases and accounts for the priming of tumour antigen-specific T cells. Recent data have revealed that in addition to antigen, dying cells provide inflammatory and immunogenic signals that determine the efficiency of CD8(+) T cell cross-priming...
March 13, 2017: Nature Reviews. Immunology
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