Review Article Heat Shock Proteins and Regulatory T Cells (original) (raw)
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Heat Shock Proteins and Regulatory T Cells
Autoimmune Diseases, 2013
Heat shock proteins (HSPs) are important molecules required for ideal protein function. Extensive research on the functional properties of HSPs indicates that HSPs may be implicated in a wide range of physiological functions including immune function. In the immune system, HSPs are involved in cell proliferation, differentiation, cytokine release, and apoptosis. Therefore, the ability of the immune system, in particular immune cells, to function optimally and in unison with other physiological systems is in part dependent on signaling transduction processes, including bidirectional communication with HSPs. Regulatory T cells (Tregs) are important T cells with suppressive functions and impairments in their function have been associated with a number of autoimmune disorders. The purpose of this paper is to examine the relationship between HSPs and Tregs. The interrelationship between cells and proteins may be important in cellular functions necessary for cell survival and expansion du...
Heat Shock Proteins as Immunomodulants
Molecules, 2018
Heat shock proteins (Hsps) are conserved molecules whose main role is to facilitate folding of other proteins. Most Hsps are generally stress-inducible as they play a particularly important cytoprotective role in cells exposed to stressful conditions. Initially, Hsps were generally thought to occur intracellulary. However, recent work has shown that some Hsps are secreted to the cell exterior particularly in response to stress. For this reason, they are generally regarded as danger signaling biomarkers. In this way, they prompt the immune system to react to prevailing adverse cellular conditions. For example, their enhanced secretion by cancer cells facilitate targeting of these cells by natural killer cells. Notably, Hsps are implicated in both pro-inflammatory and anti-inflammatory responses. Their effects on immune cells depends on a number of aspects such as concentration of the respective Hsp species. In addition, various Hsp species exert unique effects on immune cells. Becaus...
Heat shock proteins induce T cell regulation of chronic inflammation
Annals of the Rheumatic Diseases, 2006
| Immune responses to certain heat-shock proteins (HSPs) develop in almost all inflammatory diseases; however, the significance of such responses is only now becoming clear. In experimental disease models, HSPs can prevent or arrest inflammatory damage, and in initial clinical trials in patients with chronic inflammatory disease, HSP-derived peptides have been shown to promote the production of anti-inflammatory cytokines, indicating that HSPs have immunoregulatory potential. In this Review, we discuss the unique characteristics of HSPs that endow them with these immunoregulatory qualities.
Annals of the New York Academy of Sciences, 2007
Especially since the (re-)discovery of T cell subpopulations with specialized regulatory activities, mechanisms of anti-inflammatory T cell regulation are studied very actively and are expected to lead to the development of novel immunotherapeutic approaches, especially in chronic inflammatory diseases. Heat shock proteins (Hsp) are possible targets for regulatory T cells due to their enhanced expression in inflamed (stressed) tissues and the evidence that Hsp induce anti-inflammatory immunoregulatory T cell responses. Initial evidence for an immunoregulatory role of Hsp in chronic inflammation was obtained through analysis of T cell responses in the rat model of adjuvant arthritis and the findings that Hsp immunizations protected against the induction of various forms of autoimmune arthritis in rat and mouse models. Since then, immune reactivity to Hsp was found to result from inflammation in various disease models and human inflammatory conditions, such as rheumatoid arthritis (RA), type 1 diabetes, and atherosclerosis. Now, also in the light of a growing interest in T cell regulation, it is of interest to further explore the mechanisms through which Hsp can be utilized to trigger immunoregulatory pathways, capable of suppressing such a wide and diversified spectrum of inflammatory diseases.
Heat Shock Proteins in Health and Disease
2017
Heat shock or stress proteins have been regarded as intracellular molecules that have a range of housekeeping and cytoprotective functions, only being released into the extracellular environment in pathological situations such as necrotic cell death. However, evidence is now accumulating to indicate that, under certain circumstances, these proteins can be released from cells in the absence of cellular necrosis, and that extracellular heat shock proteins have a range of immunoregulatory activities. The capacity of heat shock proteins to induce pro-inflammatory responses, together with the phylogenetic similarity between prokaryotic and eukaryotic heat shock proteins, has led to the proposition that these proteins provide a link between infection and autoimmune disease. Indeed, both elevated levels of antibodies to heat shock proteins and an enhanced immune reactivity to heat shock proteins have been noted in a variety of pathogenic disease states. However, further evaluation of heat shock protein reactivity in autoimmune disease and after transplantation has shown that, rather than promoting disease, reactivity to self-heat shock proteins can downregulate the disease process. It might be that self-reactivity to heat shock proteins is a physiological response that regulates the development and progression of proinflammatory immunity to these ubiquitously expressed molecules. The evolving evidence that heat shock proteins are present in the extracellular environment, that reactivity to heat shock proteins does not necessarily reflect adverse, pro-inflammatory responses and that the promotion of reactivity to self-heat shock proteins can downregulate pathogenic processes all suggest a potential role for heat shock proteins as therapeutic agents, rather than as therapeutic targets.
The link between small heat shock proteins and the immune system
The International Journal of Biochemistry & Cell Biology, 2012
There is now compelling evidence that members of the family of small heat shock proteins (HSP) can be secreted by a variety of different types of cells. Secretion of small HSP may at times represent altruistic delivery of supporting and stabilizing factors from one cell to another. A probably more general effect of extracellular small HSP, however, is exerted by their ability to activate macrophages and macrophage-like cells. When doing so, small HSP induce an immune-regulatory state of activation, stimulating macrophages to suppress inflammation. For this reason, small HSP deserve consideration as broadly applicable therapeutic agents for inflammatory disorders.
Regulatory role of heat shock protein-specific T cells in host defense
Nagoya journal of medical science, 1992
During infection with L.monocytogenes, a facultative intracellular bacteria, TcR gamma/delta T cells specific for 65 kd hsp precede TcR alpha/beta T cells specific for the listerial antigens in appearance. The gamma/delta T cells provide a first line of defense against the infection by recognizing exogenous and endogenous 65 kd hsp on infected cells and producing cytokines such as gamma IFN. The hsp-specific T cells respond quickly to antigenically diverse pathogens before antigen-specific T cells expand clonally, and they play a role in covering the gap between the phagocytic system and highly evolved immune response. 65 kd hsp-specific T cells play important roles not only in host defense mechanism against infection with various pathogens but also in induction of auto-immune disease. Both 65 kd hsp-specific gamma delta T cells and 65 kd hsp-specific alpha beta T cells abrogate the unresponsiveness of the self-reactive alpha beta T cells and/or B cells by producing IL-2 and contrib...
Session 10: Heat‐shock proteins and immunity
Immunology, 2004
Pathogen-associated molecules are thought to act as danger signals that play a critical instructive role in generating antigen-specific adaptive immune responses. Growing evidence suggests that host tissues release endogenous danger signals in response to injury or stress that can also promote inflammation and adaptive immunity. Heat shock proteins (HSPs), induced by cellular stress or fever-range temperatures and released during necrotic cell death, are candidate endogenous danger signals that have been shown to have potent stimulatory activity on antigen-presenting cell function and induction of antigen-specific T cell responses. We have found that mammalian Hsp70 alters the response to intravenous self-peptide administration, converting tolerance to autoimmune activation in a transgenic mouse model of autoimmune diabetes. To further investigate the role of HSPs as endogenous danger signals we have used transgenic mice expressing bovine Hsc70 in the pancreatic islet beta cells. The effects of elevated pancreatic Hsc70 expression on activation of self antigen-specific T cells and development of autoimmunity will be presented.
Heat shock proteins: the fountainhead of innate and adaptive immune responses
Cell Stress & Chaperones, 2000
The ability of heat shock proteins to (1) chaperone peptides, including antigenic peptides; (2) interact with antigen-presenting cells through a receptor; (3) stimulate antigen-presenting cells to secrete inflammatory cytokines; and (4) mediate maturation of dendritic cells, makes them a unique starting point for generation of immune responses. These properties also permit the use of heat shock proteins for development of a new generation of prophylactic and therapeutic vaccines against cancers and infectious diseases.