Cellular senescence impact on immune cell fate and function

AbstractTissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function.

Download Full-text

Mitochondrial fidelity and metabolic agility control immune cell fate and function

Journal of Clinical Investigation ◽

10.1172/jci120845 ◽

2018 ◽

Vol 128 (9) ◽

pp. 3651-3661 ◽

Cited By ~ 8

Author(s):

Michael N. Sack

Keyword(s):

Cell Fate ◽

Immune Cell ◽

And Function

Download Full-text

Chapter 4 Micromanagers of Immune Cell Fate and Function

Advances in Immunology ◽

10.1016/s0065-2776(09)01204-8 ◽

2009 ◽

pp. 227-244 ◽

Cited By ~ 11

Author(s):

Fabio Petrocca ◽

Judy Lieberman

Keyword(s):

Cell Fate ◽

Immune Cell ◽

And Function

Download Full-text

Tissue adaptation: Implications for gut immunity and tolerance

Journal of Experimental Medicine ◽

10.1084/jem.20162014 ◽

2017 ◽

Vol 214 (5) ◽

pp. 1211-1226 ◽

Cited By ~ 20

Author(s):

Ana M.C. Faria ◽

Bernardo S. Reis ◽

Daniel Mucida

Keyword(s):

Cell Fate ◽

Immune Cells ◽

Immune Cell ◽

The Body ◽

Related Factors ◽

Natural Stimulation ◽

Gut Immunity ◽

Gut Mucosa ◽

And Function ◽

Intrinsic Component

Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function.

Download Full-text

Butyrate Shapes Immune Cell Fate and Function in Allergic Asthma

Frontiers in Immunology ◽

10.3389/fimmu.2021.628453 ◽

2021 ◽

Vol 12 ◽

Author(s):

William Yip ◽

Michael R. Hughes ◽

Yicong Li ◽

Alissa Cait ◽

Martin Hirst ◽

...

Keyword(s):

Allergic Asthma ◽

Cell Fate ◽

Immune Cell ◽

Inflammatory Responses ◽

Regulation Of Gene Expression ◽

Airway Disease ◽

Short Chain Fatty Acids ◽

Allergic Airway Disease ◽

Intestinal Microbiome ◽

And Function

The microbiome plays a fundamental role in how the immune system develops and how inflammatory responses are shaped and regulated. The “gut-lung axis” is a relatively new term that highlights a crucial biological crosstalk between the intestinal microbiome and lung. A growing body of literature suggests that dysbiosis, perturbation of the gut microbiome, is a driving force behind the development, and severity of allergic asthma. Animal models have given researchers new insights into how gut microbe-derived components and metabolites, such as short-chain fatty acids (SCFAs), influence the development of asthma. While the full understanding of how SCFAs influence allergic airway disease remains obscure, a recurring theme of epigenetic regulation of gene expression in several immune cell compartments is emerging. This review will address our current understanding of how SCFAs, and specifically butyrate, orchestrates cell behavior, and epigenetic changes and will provide a detailed overview of the effects of these modifications on immune cells in the context of allergic airway disease.

Download Full-text

Lactate Is a Metabolic Mediator That Shapes Immune Cell Fate and Function

Frontiers in Physiology ◽

10.3389/fphys.2021.688485 ◽

2021 ◽

Vol 12 ◽

Author(s):

Heather L. Caslin ◽

Daniel Abebayehu ◽

Julia A. Pinette ◽

John J. Ryan

Keyword(s):

Cell Fate ◽

Immune Cell ◽

Cell Types ◽

Cell Receptor ◽

Substantial Impact ◽

Specific Effects ◽

Th 17 ◽

Lactate Levels ◽

And Function

Lactate and the associated H+ ions are still introduced in many biochemistry and general biology textbooks and courses as a metabolic by-product within fast or oxygen-independent glycolysis. However, the role of lactate as a fuel source has been well-appreciated in the field of physiology, and the role of lactate as a metabolic feedback regulator and distinct signaling molecule is beginning to gain traction in the field of immunology. We now know that while lactate and the associated H+ ions are generally immunosuppressive negative regulators, there are cell, receptor, mediator, and microenvironment-specific effects that augment T helper (Th)17, macrophage (M)2, tumor-associated macrophage, and neutrophil functions. Moreover, we are beginning to uncover how lactate and H+ utilize different transporters and signaling cascades in various immune cell types. These immunomodulatory effects may have a substantial impact in cancer, sepsis, autoimmunity, wound healing, and other immunomodulatory conditions with elevated lactate levels. In this article, we summarize the known effects of lactate and H+ on immune cells to hypothesize potential explanations for the divergent inflammatory vs. anti-inflammatory effects.

Download Full-text

Molecular Chaperones: Molecular Assembly Line Brings Metabolism and Immunity in Shape

Metabolites ◽

10.3390/metabo10100394 ◽

2020 ◽

Vol 10 (10) ◽

pp. 394

Author(s):

Haoxin Zhao ◽

Lydia N. Raines ◽

Stanley Ching-Cheng Huang

Keyword(s):

Immune Responses ◽

Cell Fate ◽

Molecular Chaperones ◽

Metabolic Pathways ◽

Elevated Temperatures ◽

Immune Cell ◽

Epigenetic Modification ◽

Molecular Assembly ◽

Immune Functions ◽

And Function

Molecular chaperones are a set of conserved proteins that have evolved to assist the folding of many newly synthesized proteins by preventing their misfolding under conditions such as elevated temperatures, hypoxia, acidosis and nutrient deprivation. Molecular chaperones belong to the heat shock protein (HSP) family. They have been identified as important participants in immune functions including antigen presentation, immunostimulation and immunomodulation, and play crucial roles in metabolic rewiring and epigenetic circuits. Growing evidence has accumulated to indicate that metabolic pathways and their metabolites influence the function of immune cells and can alter transcriptional activity through epigenetic modification of (de)methylation and (de)acetylation. However, whether molecular chaperones can regulate metabolic programs to influence immune activity is still largely unclear. In this review, we discuss the available data on the biological function of molecular chaperones to immune responses during inflammation, with a specific focus on the interplay between molecular chaperones and metabolic pathways that drive immune cell fate and function.

Download Full-text