Faculty Opinions recommendation of Complement Regulates Nutrient Influx and Metabolic Reprogramming during Th1 Cell Responses.

2017 ◽  
Author(s):  
Paula Oliver
Keyword(s):  
Metabolic Reprogramming ◽  
Th1 Cell ◽  
Cell Responses ◽  
Nutrient Influx

scholarly journals Complement Regulates Nutrient Influx and Metabolic Reprogramming during Th1 Cell Responses

Immunity ◽  
2015 ◽  
Vol 42 (6) ◽  
pp. 1033-1047 ◽  
Author(s):  
Martin Kolev ◽  
Sarah Dimeloe ◽  
Gaelle Le Friec ◽  
Alexander Navarini ◽  
Giuseppina Arbore ◽  
...  
Keyword(s):  
Metabolic Reprogramming ◽  
Th1 Cell ◽  
Cell Responses ◽  
Nutrient Influx

scholarly journals Role of dendritic cell metabolic reprogramming in tumor immune evasion

2020 ◽  
Vol 32 (7) ◽  
pp. 485-491 ◽  
Author(s):  
Michael P Plebanek ◽  
Michael Sturdivant ◽  
Nicholas C DeVito ◽  
Brent A Hanks
Keyword(s):  
Dendritic Cell ◽  
Metabolic Pathways ◽  
Checkpoint Inhibitor ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Combination Immunotherapy ◽  
Tumor Immune Evasion ◽  
Effector T Cell ◽  
Cell Responses

Abstract The dendritic cell (DC) is recognized as a vital mediator of anti-tumor immunity. More recent studies have also demonstrated the important role of DCs in the generation of effective responses to checkpoint inhibitor immunotherapy. Metabolic programming of DCs dictates their functionality and can determine which DCs become immunostimulatory versus those that develop a tolerized phenotype capable of actively suppressing effector T-cell responses to cancers. As a result, there is great interest in understanding what mechanisms have evolved in cancers to alter these metabolic pathways, thereby allowing for their continued progression and metastasis. The therapeutic strategies developed to reverse these processes of DC tolerization in the tumor microenvironment represent promising candidates for future testing in combination immunotherapy clinical trials.

scholarly journals IL-23-dependent IL-17 drives Th1-cell responses followingMycobacterium bovisBCG vaccination

2011 ◽  
Vol 42 (2) ◽  
pp. 364-373 ◽  
Author(s):  
Radha Gopal ◽  
Yinyao Lin ◽  
Nataša Obermajer ◽  
Samantha Slight ◽  
Nikhil Nuthalapati ◽  
...  
Keyword(s):  
Th1 Cell ◽  
Cell Responses

scholarly journals Synovial Fibroblasts Selectively Suppress Th1 Cell Responses through IDO1-Mediated Tryptophan Catabolism

2017 ◽  
Vol 198 (8) ◽  
pp. 3109-3117 ◽  
Author(s):  
Lars-Oliver Tykocinski ◽  
Anna M. Lauffer ◽  
Antonia Bohnen ◽  
Nathalie-Christin Kaul ◽  
Stefan Krienke ◽  
...  
Keyword(s):  
Synovial Fibroblasts ◽  
Th1 Cell ◽  
Cell Responses ◽  
Tryptophan Catabolism

scholarly journals Contribution of Asparagine Catabolism to Salmonella Virulence

2016 ◽  
Vol 85 (2) ◽  
Author(s):  
Patrick A. McLaughlin ◽  
Michael McClelland ◽  
Hee-Jeong Yang ◽  
Steffen Porwollik ◽  
Lydia Bogomolnaya ◽  
...  
Keyword(s):  
T Cell ◽  
Pathogenic Bacteria ◽  
Protein A ◽  
Metabolic Reprogramming ◽  
Wild Type ◽  
Content Type ◽  
Cell Responses ◽  
Serovar Typhimurium ◽  
Salmonella Virulence ◽  
And Function

ABSTRACT Salmonellae are pathogenic bacteria that cause significant morbidity and mortality in humans worldwide. Salmonellae establish infection and avoid clearance by the immune system by mechanisms that are not well understood. We previously showed that l-asparaginase II produced by Salmonella enterica serovar Typhimurium (S. Typhimurium) inhibits T cell responses and mediates virulence. In addition, we previously showed that asparagine deprivation such as that mediated by l-asparaginase II of S. Typhimurium causes suppression of activation-induced T cell metabolic reprogramming. Here, we report that STM3997, which encodes a homolog of disulfide bond protein A (dsbA) of Escherichia coli, is required for l-asparaginase II stability and function. Furthermore, we report that l-asparaginase II localizes primarily to the periplasm and acts together with l-asparaginase I to provide S. Typhimurium the ability to catabolize asparagine and assimilate nitrogen. Importantly, we determined that, in a murine model of infection, S. Typhimurium lacking both l-asparaginase I and II genes competes poorly with wild-type S. Typhimurium for colonization of target tissues. Collectively, these results indicate that asparagine catabolism contributes to S. Typhimurium virulence, providing new insights into the competition for nutrients at the host-pathogen interface.

scholarly journals IL-1 Receptor-Associated Kinase 4 Is Essential for IL-18-Mediated NK and Th1 Cell Responses

2003 ◽  
Vol 170 (8) ◽  
pp. 4031-4035 ◽  
Author(s):  
Nobutaka Suzuki ◽  
Nien-Jung Chen ◽  
Douglas G. Millar ◽  
Shinobu Suzuki ◽  
Thomas Horacek ◽  
...  
Keyword(s):  
Th1 Cell ◽  
Cell Responses

scholarly journals The Effects of Trained Innate Immunity on T Cell Responses; Clinical Implications and Knowledge Gaps for Future Research

2021 ◽  
Vol 12 ◽  
Author(s):  
Dearbhla M. Murphy ◽  
Kingston H. G. Mills ◽  
Sharee A. Basdeo
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cells ◽  
T Cell Responses ◽  
Innate Immune ◽  
Metabolic Reprogramming ◽  
Innate Immune Cells ◽  
Peripheral Tissues ◽  
Trained Immunity ◽  
Cell Responses

The burgeoning field of innate immune training, also called trained immunity, has given immunologists new insights into the role of innate responses in protection against infection and in modulating inflammation. Moreover, it has led to a paradigm shift in the way we think about immune memory and the interplay between innate and adaptive immune systems in conferring immunity against pathogens. Trained immunity is the term used to describe the medium-term epigenetic and metabolic reprogramming of innate immune cells in peripheral tissues or in the bone marrow stem cell niche. It is elicited by an initial challenge, followed by a significant period of rest that results in an altered response to a subsequent, unrelated challenge. Trained immunity can be associated with increased production of proinflammatory mediators, such as IL-1β, TNF and IL-6, and increased expression of markers on innate immune cells associated with antigen presentation to T cells. The microenvironment created by trained innate immune cells during the secondary challenge may have profound effects on T cell responses, such as altering the differentiation, polarisation and function of T cell subtypes, including Th17 cells. In addition, the Th1 cytokine IFN-γ plays a critical role in establishing trained immunity. In this review, we discuss the evidence that trained immunity impacts on or can be impacted by T cells. Understanding the interplay between innate immune training and how it effects adaptive immunity will give insights into how this phenomenon may affect the development or progression of disease and how it could be exploited for therapeutic interventions or to enhance vaccine efficacy.

scholarly journals Glycolysis Inhibition Induces Functional and Metabolic Exhaustion of CD4+ T Cells in Type 1 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Christina P. Martins ◽  
Lee A. New ◽  
Erin C. O’Connor ◽  
Dana M. Previte ◽  
Kasey R. Cargill ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Cell Function ◽  
T Cell Responses ◽  
Metabolic Reprogramming ◽  
Cell Responses ◽  
T Cell Function

In Type 1 Diabetes (T1D), CD4+ T cells initiate autoimmune attack of pancreatic islet β cells. Importantly, bioenergetic programs dictate T cell function, with specific pathways required for progression through the T cell lifecycle. During activation, CD4+ T cells undergo metabolic reprogramming to the less efficient aerobic glycolysis, similarly to highly proliferative cancer cells. In an effort to limit tumor growth in cancer, use of glycolytic inhibitors have been successfully employed in preclinical and clinical studies. This strategy has also been utilized to suppress T cell responses in autoimmune diseases like Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), and Rheumatoid Arthritis (RA). However, modulating T cell metabolism in the context of T1D has remained an understudied therapeutic opportunity. In this study, we utilized the small molecule PFK15, a competitive inhibitor of the rate limiting glycolysis enzyme 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase 3 (PFKFB3). Our results confirmed PFK15 inhibited glycolysis utilization by diabetogenic CD4+ T cells and reduced T cell responses to β cell antigen in vitro. In an adoptive transfer model of T1D, PFK15 treatment delayed diabetes onset, with 57% of animals remaining euglycemic at the end of the study period. Protection was due to induction of a hyporesponsive T cell phenotype, characterized by increased and sustained expression of the checkpoint molecules PD-1 and LAG-3 and downstream functional and metabolic exhaustion. Glycolysis inhibition terminally exhausted diabetogenic CD4+ T cells, which was irreversible through restimulation or checkpoint blockade in vitro and in vivo. In sum, our results demonstrate a novel therapeutic strategy to control aberrant T cell responses by exploiting the metabolic reprogramming of these cells during T1D. Moreover, the data presented here highlight a key role for nutrient availability in fueling T cell function and has implications in our understanding of T cell biology in chronic infection, cancer, and autoimmunity.

scholarly journals Helicobacter pylori-Induced Th17 Responses Modulate Th1 Cell Responses, Benefit Bacterial Growth, and Contribute to Pathology in Mice

2010 ◽  
Vol 184 (9) ◽  
pp. 5121-5129 ◽  
Author(s):  
Yun Shi ◽  
Xiao-Fei Liu ◽  
Yuan Zhuang ◽  
Jin-Yu Zhang ◽  
Tao Liu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Growth ◽  
Th1 Cell ◽  
Cell Responses
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