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mtor immunology

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https://www.readbyqxmd.com/read/30055922/nutrient-sensing-kinase-signaling-in-bovine-immune-cells-is-altered-during-the-postpartum-nutrient-deficit-a-possible-role-in-transition-cow-inflammatory-response
#1
S Mann, A Sipka, F A Leal Yepes, D V Nydam, T R Overton, J J Wakshlag
Transition dairy cows experience a nutrient deficit, particularly in the immediate postpartum period. At the same time, the inflammatory balance is altered and cows exhibit an immune response primed for inflammatory response rather than tolerance. The mechanistic link that might be underlying the immunological effects due to the lack in nutrients is not fully understood. Studies in other species demonstrate an orchestrating role of nutrient-sensing kinases in the determination of immune phenotypes and immune cell proliferation and differentiation...
July 25, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/30055803/autophagy-is-involved-in-acetylshikonin-ameliorating-non-alcoholic-steatohepatitis-through-ampk-mtor-pathway
#2
Jiacheng Zeng, Banghao Zhu, Meiling Su
Acetylshikonin (AS), a naphthoquinone constituent derived from Lithospermum erythrorhizon, has been revealed various pharmacological activities including anti-oxidative, anti-inflammatory and antifertility effects. Our previous study has illuminated the effects of AS on preventing obesity and hepatic steatosis in db/db mice. However, the effects of AS and the molecular mechanisms for curing non-alcoholic steatohepatitis (NASH) have not yet been studied. Autophagy has been considered as a lysosomal degradative pathway responsible for the removal of cellular lipid droplets through a process called lipophagy, which is recognized as a potential therapeutic approach for NASH...
July 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30022363/ppar%C3%AE-agonist-pgz-attenuates-ova-induced-airway-inflammation-and-airway-remodeling-via-rgs4-signaling-in-mouse-model
#3
Xia Meng, Xinrong Sun, Yonghong Zhang, Hongyang Shi, Wenjing Deng, Yanqin Liu, Guizuo Wang, Ping Fang, Shuanying Yang
Peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone (PGZ) exhibits potential protective effects in asthma. Recently, regulator of G protein 4 (RGS4) has been reported to be associated with immunological and inflammatory responses. However, no evidence has shown the influence of PPARγ on RGS4 expression in airway disorders. In this study, BALB/c mice received ovalbumin (OVA) sensitization followed by OVA intranasal challenge for 90 days to establish a chronic asthma mouse model. Accompanied with OVA challenge, the mice received administration of PPARγ agonist PGZ (10 mg/kg) intragastrically or RGS4 inhibitor CCG 63802 (0...
July 19, 2018: Inflammation
https://www.readbyqxmd.com/read/29961151/mast-cells-participate-in-allograft-rejection-can-il-37-play-an-inhibitory-role
#4
REVIEW
Pio Conti, Alessandro Caraffa, Gianpaolo Ronconi, Spiros K Kritas, Filiberto Mastrangelo, Lucia Tettamanti, Ilias Frydas, Theoharis C Theoharides
OBJECTIVE: The aim of this study was to evaluate the role of mast cells (MCs) in allograft rejection, eventually inhibited by IL-37. Immune cells including MCs participate in allograft rejection by generating IL-1, IL-33, TNF and other cytokines. METHODS: We evaluated allograft rejection on the experience of our experimental data and using the relevant literature. RESULTS: MCs are involved in initiation and regulation of innate and adaptive immune responses-pathways...
June 30, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29915171/effects-of-immune-suppression-for-transplantation-on-inflammatory-colorectal-cancer-progression
#5
Imerio Angriman, Lucrezia Furian, Melania Scarpa, Matteo Fassan, Susan Morgan, Andrea Porzionato, Andromachi Kotsafti, Luca Saadeh, Cristina Silvestre, Raffaele De Caro, Amedeo Carraro, Umberto Tedeschi, Romeo Bardini, Paolo Rigotti, Massimo Rugge, Carlo Castoro, Ignazio Castagliuolo, Marco Scarpa
BACKGROUND: Ulcerative colitis patients and transplant recipients are at risk for colorectal cancer. Here, we show that immunosuppressive regimens for kidney transplants are associated with the progression of ulcerative colitis-related carcinogenesis. METHODS: We describe the case of a patient diagnosed with colorectal cancer in ulcerative colitis while on immunosuppressive therapy for a kidney transplant. The immunological microenvironment of the cancer and its mutational status were analyzed, and a mouse colon cancer model was created to replicate the unique clinical conditions...
June 19, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29901635/rapamycin-treatment-for-amyotrophic-lateral-sclerosis-protocol-for-a-phase-ii-randomized-double-blind-placebo-controlled-multicenter-clinical-trial-rap-als-trial
#6
RANDOMIZED CONTROLLED TRIAL
Jessica Mandrioli, Roberto D'Amico, Elisabetta Zucchi, Annalisa Gessani, Nicola Fini, Antonio Fasano, Claudia Caponnetto, Adriano Chiò, Eleonora Dalla Bella, Christian Lunetta, Letizia Mazzini, Kalliopi Marinou, Gianni Sorarù, Sara de Biasi, Domenico Lo Tartaro, Marcello Pinti, Andrea Cossarizza
INTRODUCTION: Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29867948/-immune-tor-opathies-a-novel-disease-entity-in-clinical-immunology
#7
REVIEW
Sophie Jung, Laura Gámez-Díaz, Michele Proietti, Bodo Grimbacher
Primary immunodeficiencies (PIDs) represent a group of mostly monogenic disorders caused by loss- or gain-of-function mutations in over 340 known genes that lead to abnormalities in the development and/or the function of the immune system. However, mutations in different genes can affect the same cell-signaling pathway and result in overlapping clinical phenotypes. In particular, mutations in the genes encoding for members of the phosphoinositide3-kinase (PI3K)/AKT/mTOR/S6 kinase (S6K) signaling cascade or for molecules interacting with this pathway have been associated with different PIDs that are often characterized by the coexistence of both immune deficiency and autoimmunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29741731/expression-of-grim-19-in-unexplained-recurrent-spontaneous-abortion-and-possible-pathogenesis
#8
Yang Yang, Laiyang Cheng, Xiaohui Deng, Hongling Yu, Lan Chao
STUDY QUESTION: Is aberrant expression of gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) associated with unexplained recurrent spontaneous abortion (URSA)? SUMMARY ANSWER: GRIM-19 deficiency may regulate regulatory T cell/T helper 17 cell (Treg/Th17) balance partly through reactive oxygen species (ROS)-mammalian target of rapamycin (mTOR) signaling axis in URSA. WHAT IS KNOWN ALREADY: Immunological disorders may cause impaired maternal immune tolerance to the fetus and result in fetal rejection...
July 1, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29728568/egr2-independent-klf1-mediated-induction-of-pd-l1-in-cd4-t-cells
#9
Shuzo Teruya, Tomohisa Okamura, Toshihiko Komai, Mariko Inoue, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Programmed death ligand 1 (PD-L1)-mediated induction of immune tolerance has been vigorously investigated in autoimmunity and anti-tumor immunity. However, details of the mechanism by which PD-L1 is induced in CD4+ T cells are unknown. Here, we revealed the potential function of Klf1 and Egr2-mediated induction of PD-L1 in CD4+ T cells. We focused on the molecules specifically expressed in CD4+ CD25- LAG3+ regulatory T cells (LAG3+ Tregs) highly express of PD-L1 and transcription factor Egr2. Although ectopic expression of Egr2 induced PD-L1, a deficiency of Egr2 did not affect its expression, indicating the involvement of another PD-L1 induction mechanism...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29578532/critical-role-of-ox40-signaling-in-the-tcr-independent-phase-of-human-and-murine-thymic-treg-generation
#10
Prabhakaran Kumar, Alejandra Marinelarena, Divya Raghunathan, Vandhana K Ragothaman, Shikha Saini, Palash Bhattacharya, Jilao Fan, Alan L Epstein, Ajay V Maker, Bellur S Prabhakar
Regulatory T cells (Tregs) play a pivotal role in immune-tolerance, and loss of Treg function can lead to the development of autoimmunity. Natural Tregs generated in the thymus substantially contribute to the Treg pool in the periphery, where they suppress self-reactive effector T cells (Teff) responses. Recently, we showed that OX40L (TNFSF4) is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation (CAP-independent) in the presence of low-dose IL-2. Therefore, we hypothesized that OX40 signaling might be integral to the TCR-independent phase of murine and human thymic Treg (tTreg) development...
March 26, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29532571/sirolimus-as-an-alternative-treatment-in-patients-with-granulomatous-lymphocytic-lung-disease-and-humoral-immunodeficiency-with-impaired-regulatory-t-cells
#11
Angela Deyà-Martínez, Ana Esteve-Solé, Natalia Vélez-Tirado, Veronica Celis, Jordi Costa, Maria Cols, Cristina Jou, Alexandru Vlagea, Ana María Plaza-Martin, Manel Juan, Laia Alsina
BACKGROUND: One of the most frequent non-infectious complications of humoral immunodeficiencies with a CVID-like pattern is a particular form of inflammatory lung disease which is called granulomatous-lymphocytic interstitial lung disease (GLILD). Its development worsens patient prognosis, with a significant decrease in survival. Currently, there are no unified guidelines regarding its management, and different combinations of immunosuppressants have been used with variable success. METHODS: Clinical and radiological data were collected from patient's medical charts...
June 2018: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/29411774/gpr43-mediates-microbiota-metabolite-scfa-regulation-of-antimicrobial-peptide-expression-in-intestinal-epithelial-cells-via-activation-of-mtor-and-stat3
#12
Ye Zhao, Feidi Chen, Wei Wu, Mingming Sun, Anthony J Bilotta, Suxia Yao, Yi Xiao, Xiangsheng Huang, Tonyia D Eaves-Pyles, George Golovko, Yuriy Fofanov, Warren D'Souza, Qihong Zhao, Zhanju Liu, Yingzi Cong
The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIIIγ and certain defensins. However, the mechanisms involved are still not completely understood. In this report, we found that IEC expression levels of RegIIIγ and β-defensins 1, 3, and 4 were lower in G protein-coupled receptor (GPR)43-/- mice compared to that of wild-type (WT) mice...
May 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29408453/a-randomized-control-trial-to-establish-the-feasibility-and-safety-of-rapamycin-treatment-in-an-older-human-cohort-immunological-physical-performance-and-cognitive-effects
#13
Ellen Kraig, Leslie A Linehan, Hanyu Liang, Terry Q Romo, Qianqian Liu, Yubo Wu, Adriana D Benavides, Tyler J Curiel, Martin A Javors, Nicolas Musi, Laura Chiodo, Wouter Koek, Jonathan A L Gelfond, Dean L Kellogg
Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals, suggesting that mTOR inhibition could potentially slow the progression of aging-associated pathologies in older humans (Harrison et al., 2009; Miller et al., 2011). However, the safety and tolerability of RAPA in older human subjects have not yet been demonstrated...
May 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29408410/the-role-of-mtor-mediated-signaling-in-the-regulation-of-cellular-migration
#14
REVIEW
Ailsa K Holroyd, Alison M Michie
Mechanistic target for rapamycin (mTOR) is a serine/threonine protein kinase that forms two distinct complexes mTORC1 and mTORC2, integrating mitogen and nutrient signals to regulate cell survival and proliferation; processes which are commonly deregulated in human cancers. mTORC1 and mTORC2 have divergent molecular associations and cellular functions: mTORC1 regulates in mRNA translation and protein synthesis, while mTORC2 is involved in the regulation of cellular survival and metabolism. Through AKT phosphorylation/activation, mTORC2 has also been reported to regulate cell migration...
April 2018: Immunology Letters
https://www.readbyqxmd.com/read/29400578/the-immune-system-as-a-chronotoxicity-target-of-the-anticancer-mtor-inhibitor-everolimus
#15
Narin Ozturk, Dilek Ozturk, Zeliha Pala-Kara, Engin Kaptan, Serap Sancar-Bas, Nurten Ozsoy, Suzan Cinar, Gunnur Deniz, Xiao-Mei Li, Sylvie Giacchetti, Francis Lévi, Alper Okyar
The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing...
May 2018: Chronobiology International
https://www.readbyqxmd.com/read/29328908/metabolic-induction-of-trained-immunity-through-the-mevalonate-pathway
#16
Siroon Bekkering, Rob J W Arts, Boris Novakovic, Ioannis Kourtzelis, Charlotte D C C van der Heijden, Yang Li, Calin D Popa, Rob Ter Horst, Julia van Tuijl, Romana T Netea-Maier, Frank L van de Veerdonk, Triantafyllos Chavakis, Leo A B Joosten, Jos W M van der Meer, Henk Stunnenberg, Niels P Riksen, Mihai G Netea
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29297752/il4-interleukin-4-induces-autophagy-in-b-cells-leading-to-exacerbated-asthma
#17
Fucan Xia, Changwen Deng, Yanyan Jiang, Yulan Qu, Jiewen Deng, Zhijian Cai, Yuanyuan Ding, Zhenhong Guo, Jianli Wang
Allergic asthma is a common airway inflammatory disease in which B cells play important roles through IgE production and antigen presentation. SNP (single nucleotide polymorphism) analysis showed that Atg (autophagy-related) allele mutations are involved in asthma. It has been demonstrated that macroautophagy/autophagy is essential for B cell survival, plasma cell differentiation and immunological memory maintenance. However, whether B cell autophagy participates in asthma pathogenesis remains to be investigated...
2018: Autophagy
https://www.readbyqxmd.com/read/29209321/consumption-of-diet-containing-free-amino-acids-exacerbates-colitis-in-mice
#18
Adna Luciana Souza, Sarah Leão Fiorini Aguiar, Mariana Camila Gonçalves Miranda, Luisa Lemos, Mauro Andrade Freitas Guimaraes, Daniela Silva Reis, Patrícia Aparecida Vieira Barros, Emerson Soares Veloso, Toniana Gonçalves Carvalho, Fabiola Mara Ribeiro, Enio Ferreira, Denise Carmona Cara, Ana Cristina Gomes-Santos, Ana Maria Caetano Faria
Dietary proteins can influence the maturation of the immune system, particularly the gut-associated lymphoid tissue, when consumed from weaning to adulthood. Moreover, replacement of dietary proteins by amino acids at weaning has been shown to impair the generation of regulatory T cells in the gut as well as immune activities such as protective response to infection, induction of oral and nasal tolerance as well as allergic responses. Polymeric and elemental diets are used in the clinical practice, but the specific role of intact proteins and free amino acids during the intestinal inflammation are not known...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29050006/recent-insights-into-the-biological-functions-of-sestrins-in-health-and-disease
#19
REVIEW
Menglong Wang, Yao Xu, Jianfang Liu, Jing Ye, Wenhui Yuan, Huimin Jiang, Zhen Wang, Hong Jiang, Jun Wan
Sestrins (Sesns) have been identified as a family of highly conserved stress-inducible proteins that are strongly up-regulated by various stresses, including DNA damage, oxidative stress, and hypoxia. The Sesns play protective roles in most physiological and pathological conditions mainly through the regulation of oxidative stress, inflammation, autophagy, endoplasmic reticulum stress, and metabolic homeostasis. In this review, we discussed the possible regulators of Sesns expression, such as p53, forkhead box O, nuclear factor erythroid 2 like 2 (Nrf2), NH (2)-terminal kinase (JNK)/c-Jun pathway and hypoxia-inducible factor-1α (Hif-1α), and the downstream pathways regulated by the Sesns including AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, mitogen-activated protein kinases (MAPKs) signaling, Nrf2 signaling, NADPH oxidase signaling and transforming growth factor β (TGF-β) signaling in heart diseases, lung diseases, gastrointestinal tract diseases, liver and metabolism diseases, neurological diseases, kidney diseases and immunological diseases...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28988508/immunological-effects-of-everolimus-in-patients-with-metastatic-renal-cell-cancer
#20
Charlotte M Huijts, Saskia J Santegoets, Tamarah D de Jong, Henk M Verheul, Tanja D de Gruijl, Hans J van der Vliet
The mammalian target of rapamycin (mTOR) is a crucial kinase present in all cells. Besides its role in the regulation of cell-growth, proliferation, angiogenesis, and survival of malignant tumors, mTOR additionally plays an important role in immune regulation by controlling the balance between effector T cells and regulatory T cells (Tregs). This critically affects the suppressive state of the immune system. Here, the systemic immunological effects of everolimus treatment were comprehensively investigated in five patients with metastatic renal cell cancer...
December 2017: International Journal of Immunopathology and Pharmacology
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