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Immunological pathways

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https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#1
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28209523/tb-iris-proteomic-analysis-of-in-vitro-pbmc-responses-to-mycobacterium-tuberculosis-and-response-modulation-by-dexamethasone
#2
Liam Bell, Janique M Peyper, Shaun Garnett, Rabecca Tadokera, Robert Wilkinson, Graeme Meintjes, Jonathan M Blackburn
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) occurs in 8-54% of South African patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. Improved TB-IRIS molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. We assessed how TB-IRIS status and dexamethasone influence leukocyte proteomic responses to Mycobacterium tuberculosis (Mtb). Patient blood was obtained three weeks post-anti-retroviral therapy initiation...
February 13, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28207493/treatment-of-lupus-nephritis-current-paradigms-and-emerging-strategies
#3
Maria Dall'Era
PURPOSE OF REVIEW: Lupus nephritis is the most common organ-threatening manifestation of lupus and continues to result in end-stage renal disease. This review describes the contemporary treatment of lupus nephritis as well as emerging therapeutic strategies. RECENT FINDINGS: Lupus nephritis management consists of an initial (induction) phase and a maintenance (extended) phase in which steroids are used in combination with another immunosuppressive medication. Current treatments are incompletely effective and associated with substantial toxicity...
February 15, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28207490/how-hiv-1-entry-mechanism-and-broadly-neutralizing-antibodies-guide-structure-based-vaccine-design
#4
Marie Pancera, Anita Changela, Peter D Kwong
PURPOSE OF REVIEW: An HIV-1 vaccine that elicits broadly neutralizing antibodies (bNAbs) remains to be developed. Here, we review how knowledge of bNAbs and HIV-1 entry mechanism is guiding the structure-based design of vaccine immunogens and immunization regimens. RECENT FINDINGS: Isolation of bNAbs from HIV-1-infected donors has led to an unprecedented understanding of the sites of vulnerability that these antibodies target on the HIV-1 envelope (Env) as well as of the immunological pathways that these antibody lineages follow to develop broad and potent neutralization...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28203237/activation-of-the-wnt-pathway-by-mycobacterium-tuberculosis-a-wnt-wnt-situation
#5
REVIEW
Tomás Villaseñor, Edgardo Madrid-Paulino, Rafael Maldonado-Bravo, Antonio Urbán-Aragón, Leonor Pérez-Martínez, Gustavo Pedraza-Alva
Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against M. tuberculosis. The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28203119/higher-phagocytic-activity-of-thioglycollate-elicited-peritoneal-macrophages-is-related-to-metabolic-status-of-the-cells
#6
Sofia Pavlou, Luxi Wang, Heping Xu, Mei Chen
BACKGROUND: Peritoneal macrophages are widely used in immunological studies. The cells can be collected under non-elicited (resident) or elicited (e.g., with Brewer thioglycollate broth injection) conditions, and their phenotype and functions differ. Recent studies have shown that macrophage phenotype and function are related to their metabolic states, and metabolic reprogramming has been an emerging concept for controlling macrophage function. In this study, we examined the metabolic state of resident and elicited macrophages and investigated how their metabolic state may affect cell function, including phagocytosis...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#7
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28199198/the-immunological-function-of-gabaergic-system
#8
Chenlu Wu, Xiaobin Qin, Huihui Du, Nengzhang Li, Wenkai Ren, Yuanyi Peng
As a well-known inhibitory neurotransmitter in the central nervous system, gamma-aminobutyric acid also has critical roles in immune system. Immune cells (e.g., lymphocytes, macrophages) express the components of GABAergic system, including GABA receptors, GABA transporters, and GABA metabolic enzymes. The functions of immune cells are highly impacted on GABA signaling. GABAergic components negatively regulate the immune responses, particularly the T cell-mediated immunity, via their effects on production of pro-inflammatory cytokines and activation of signal pathways, like mitogen-activated protein kinase and nuclear factor-kappaB pathways...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28198830/-final-common-pathway-of-human-cancer-immunotherapy-targeting-random-somatic-mutations
#9
REVIEW
Eric Tran, Paul F Robbins, Steven A Rosenberg
Effective clinical cancer immunotherapies, such as administration of the cytokine IL-2, adoptive cell transfer (ACT) and the recent success of blockade of the checkpoint modulators CTLA-4 and PD-1, have been developed without clear identification of the immunogenic targets expressed by human cancers in vivo. Immunotherapy of patients with cancer through the use of ACT with autologous lymphocytes has provided an opportunity to directly investigate the antigen recognition of lymphocytes that mediate cancer regression in humans...
February 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28198364/interleukin-22-drives-nitric-oxide-dependent-dna-damage-and-dysplasia-in-a-murine-model-of-colitis-associated-cancer
#10
C Wang, G Gong, A Sheh, S Muthupalani, E M Bryant, D A Puglisi, H Holcombe, E A Conaway, N A P Parry, V Bakthavatchalu, S P Short, C S Williams, G N Wogan, S R Tannenbaum, J G Fox, B H Horwitz
The risk of colon cancer is increased in patients with Crohn's disease and ulcerative colitis. Inflammation-induced DNA damage could be an important link between inflammation and cancer, although the pathways that link inflammation and DNA damage are incompletely defined. RAG2-deficient mice infected with Helicobacter hepaticus (Hh) develop colitis that progresses to lower bowel cancer. This process depends on nitric oxide (NO), a molecule with known mutagenic potential. We have previously hypothesized that production of NO by macrophages could be essential for Hh-driven carcinogenesis, however, whether Hh infection induces DNA damage in this model and whether this depends on NO has not been determined...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28194023/interleukin-33-drives-hepatic-fibrosis-through-activation-of-hepatic-stellate-cells
#11
Zhongming Tan, Qianghui Liu, Runqiu Jiang, Long Lv, Siamak S Shoto, Isabelle Maillet, Valerie Quesniaux, Junwei Tang, Wenjie Zhang, Beicheng Sun, Bernhard Ryffel
Liver fibrosis is a consequence of chronic liver disease, causing morbidity and mortality. Interleukin-33 (IL-33) is a critical mediator of inflammation, which may be involved in the development of liver fibrosis. Here, we investigated the role of IL-33 in human patients and experimental bile-duct ligation (BDL)-induced fibrosis in mice. We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis. Liver injury, inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor, and the activation of hepatic stellate cells (HSCs) was decreased in ST2-deficient mice...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28194021/type-i-ifn-augments-il-27-dependent-trim25-expression-to-inhibit-hbv-replication
#12
Guangyun Tan, Qingfei Xiao, Hongxiao Song, Feng Ma, Fengchao Xu, Di Peng, Na Li, Xiaosong Wang, Junqi Niu, Pujun Gao, F Xiao-Feng Qin, Genhong Cheng
Hepatitis B virus (HBV) can cause chronic hepatitis B, which may lead to cirrhosis and liver cancer. Type I interferon (IFN) is an approved drug for the treatment of chronic hepatitis B. However, the fundamental mechanisms of antiviral action by type I IFN and the downstream signaling pathway are unclear. TRIM25 is an IFN-stimulated gene (ISG) that has an important role in RIG-I ubiquitination and activation. Whether TRIM25 is induced in liver cells by type I IFN to mediate anti-HBV function remains unclear...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28192189/mir-425-regulates-inflammatory-cytokine-production-in-cd4-t-cells-via-n-ras-upregulation-in-primary-biliary-cholangitis
#13
Ryo Nakagawa, Ryosuke Muroyama, Chisato Saeki, Kaku Goto, Yoshimi Kaise, Kazuhiko Koike, Masanori Nakano, Yasuo Matsubara, Keiko Takano, Sayaka Ito, Masayuki Saruta, Naoya Kato, Mikio Zeniya
BACKGROUND & AIM: Primary biliary cholangitis (PBC) is an autoimmune liver disease of unknown pathogenesis. Consequently, therapeutic targets for PBC have yet to be identified. Because CD4(+) T cells play a pivotal role in immunological dysfunction observed in PBC, we analysed microRNA (miRNA) and mRNA expression in CD4(+) T cells to investigate PBC pathogenesis and identify novel therapeutic targets. METHODS: We performed integral miRNA and mRNA analysis of 14 PBC patients and 10 healthy controls using microarray and quantitative real time polymerase chain reaction (qRT-PCR) with gene set enrichment analysis...
February 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28191593/learning-from-a-contemporary-history-of-immunology
#14
REVIEW
Melvin Cohn
This essay is a selected aspect of the history of contemporary immunology seen from a "what can we learn" point of view. It is limited to the ideas and experiments from which we might draw a take-home message. The emphasis is on the convoluted pathway that was actually used by immunologists to arrive at understanding compared to the direct pathway that could have been used given the knowledge at that time. It takes the reader through the instructionist era of the 1940s to the present by stressing the elements of thinking most conducive to the arrival at a default understanding of the intact immune system...
February 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28190773/%C3%AE-cells-that-resist-immunological-attack-develop-during-progression-of-autoimmune-diabetes-in-nod-mice
#15
Jinxiu Rui, Songyan Deng, Arnon Arazi, Ana Luisa Perdigoto, Zongzhi Liu, Kevan C Herold
Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune-mediated destruction of β cells. How β cells respond to immune attack is unknown. We identified a population of β cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal β cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of β cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes...
February 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28188716/-immunological-alterations-in-common-variable-immunodeficiency
#16
Laura Berrón-Ruiz
Common variable immunodeficiency (CVID) is the largest group of symptomatic primary immune deficiencies; it is characterized by hypogammaglobulinemia, poor response to vaccines and increased susceptibility to infections. Cellular phenotypes and abnormalities have been described both in adaptive and innate immune response. Several classifications of common variable immunodeficiency are based on defects found on T and B cells, which have been correlated with clinical manifestations. In recent years, significant progress has been made in elucidating the genetic mechanisms that result in a IDCV phenotype...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28188592/redirecting-reproductive-immunology-research-toward-pregnancy-as-a-period-of-temporary-immune-tolerance
#17
Norbert Gleicher, Vitaly A Kushnir, David H Barad
Referring to two recent publications, we here propose that clinical reproductive immunology has for decades stagnated because reproductive medicine, including assisted reproduction (AR), has failed to accept embryo implantation as an immune system-driven process, dependent on establishment of maternal tolerance toward the implanting fetal semi-allograft (and complete allograft in cases of oocyte donation). Pregnancy represents a biologically unique period of temporary (to the period of gestation restricted) tolerance, otherwise only known in association with parasitic infections...
February 10, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28183352/combined-effect-of-bcg-vaccination-and-enriched-environment-promote-neurogenesis-and-spatial-cognition-via-a-shift-in-meningeal-macrophage-m2-polarization
#18
Fangfang Qi, Zejie Zuo, Junhua Yang, Saisai Hu, Yang Yang, Qunfang Yuan, Juntao Zou, Kaihua Guo, Zhibin Yao
BACKGROUND: The spatial learning abilities of developing mice benefit from extrinsic cues, such as an enriched environment, with concomitant enhancement in cognitive functions. Interestingly, such enhancements can be further increased through intrinsic Bacillus Calmette-Guérin (BCG) vaccination. RESULTS: Here, we first report that combined neonatal BCG vaccination and exposure to an enriched environment (Enr) induced combined neurobeneficial effects, including hippocampal long-term potentiation, and increased neurogenesis and spatial learning and memory, in mice exposed to the Enr and vaccinated with BCG relative to those in the Enr that did not receive BCG vaccination...
February 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28182501/disorders-of-the-jak-stat-pathway-in-t-cell-lymphoma-pathogenesis-implications-for-immunotherapy
#19
Thomas A Waldmann, Jing Chen
Common gamma receptor-dependent cytokines and their JAK/STAT pathways play pivotal roles in T cell immunity. Abnormal activation of this system was pervasive in diverse T cell malignancies assessed by pSTAT3/pSTAT5 phosphorylation. Activating mutations were described in some but not all cases. JAK1 and STAT3 were required for proliferation and survival of these T cell lines whether or not JAKs or STATs were mutated. Activating JAK and STAT mutations were not sufficient to initiate leukemic cell proliferation but rather only augmented signals from upstream in the cytokine pathway...
February 9, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28176650/is-there-a-role-for-epigenetic-enhancement-of-immunomodulatory-approaches-to-cancer-treatment
#20
Kirsty J Flower, Sadaf Ghaem-Maghami, Robert Brown
The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance...
February 5, 2017: Current Cancer Drug Targets
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