IL-10 Is Critically Involved in Mycobacterial HSP70 Induced Suppression of Proteoglycan-Induced Arthritis

Wieten, Lotte; Berlo, Suzanne E.; Brink, Corlinda B. ten; Kooten, Peter J. S. van; Singh, Mahavir; Zee, Ruurd van der; Glant, Tibor T.; Broere, Femke; Eden, Willem van

doi:10.1371/journal.pone.0004186

Cited by 57 publications

(58 citation statements)

References 39 publications

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“…However, contrary to expectations, in several studies using animal models of arthritis (120,121), diabetes and MS (122,123) as well as in clinical trials (124), preimmunization with bacterial gp96, Hsp60 or Hsp70 abrogated the subsequently induced inflammatory disease. A study by Wieten et al demonstrated that the spread of the regulatory capacity mediated by mycobacterial Hsp70 in proteoglycan-induced arthritis (PGIA), a chronic and relapsing T-cell-mediated murine model of arthritis, is dependent on IL-10 production and on specific regulatory self-HSP-cross-reactive T cells (125). The high degree of phylogenetic similarity between Hsp60 and Hsp70 as well as the presence of Hsp60 and Hsp70 in the peripheral circulation of healthy individuals (126,127) indicates that immune responses to HSP are highly controlled and regulated.…”

Section: Molecular Mimicrymentioning

confidence: 99%

Heat Shock Protein 70: Roles in Multiple Sclerosis

Mansilla

Montalbán

Espejo

2012

Mol Med

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Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE.

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Section: Molecular Mimicrymentioning

confidence: 99%

Heat Shock Protein 70: Roles in Multiple Sclerosis

Mansilla

Montalbán

Espejo

2012

Mol Med

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“…Therefore, the presence of such T cells could be important for maintenance of selftolerance. Previously, we and others showed the immunoregulatory capacity of administration of exogenous HSP70 and HSP70-derived peptides in experimental rodent arthritis models (Tanaka et al 1999;van Herwijnen et al 2012;Wendling et al 2000;Wieten et al 2009). The presence of naturally occurring T cell responses toward HSP70 peptides presented under physiological conditions in humans is, thus far, unknown.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 94%

T cell recognition of naturally presented epitopes of self-heat shock protein 70

Jong

Koffeman

Meerding

et al. 2014

Cell Stress and Chaperones

Self Cite

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Self-reactive T cells have shown to have a potential role as regulators of the immune system preventing or even suppressing autoimmunity. One of the most abundant proteins that can be eluted from human HLA molecules is heat shock protein 70 (HSP70). The aims of the current study are to identify HSP70 epitopes based on published HLA elution studies and to investigate whether T cells from healthy individuals may respond to such self-epitopes. A literature search and subsequent in silico binding prediction based on theoretical MHC binding motifs resulted in the identification of seven HSP70 epitopes. PBMCs of healthy controls proliferated after incubation with two of the seven peptides (H167 and H290). Furthermore H161, H290, and H443 induced CD69 expression or production of cytokines IFNγ or TNFα in healthy controls. The identification of these naturally presented epitopes and the response they elicit in the normal immune system make them potential candidates to study during inflammatory conditions as well as in autoimmune diseases.

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“…For mycobacterial HSP70, disease prevention by prior HSP immunization was seen in rat adjuvant arthritis, avridine arthritis, and to a lower extent collagen II arthritis [46,57]. Recently, we also have seen preventive effects in a mouse (Balb/c) model of aggrecaninduced model using preimmunisation with mycobacterial HSP70 in DDA as an adjuvant [58].…”

Section: Hsp Induce Protection In Mouse and Rat Arthritis Modelsmentioning

confidence: 96%

Immune Recognition of Heat Shock Proteins Provides a Molecular Basis for the “Hygiene Hypothesis” Linking High Prevalence of Immune Disorders to Lack of Cell Stress Eliciting Events

Eden

2012

ISRN Immunology

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A modern interpretation of the hygiene hypothesis proposes the so-called "old friends" to trigger tolerogenic responses through innate receptors of dendritic cells (DC). Tolerogenic DCs would drive regulatory T-cell polarization through induction of oldfriend-specific Treg. In the tissues of the gut that are besieged by our old friends, these cells are held to produce a continuous bystander regulation. However, such local bystander regulation in the gut may be difficult to reconcile with suppression of responses to airway allergens or autoimmune antigens present in distant body tissues. Alternatively, the regulatory Tregs may be triggered through recognition of stress proteins or heat shock proteins (HSP). Microbial HSP are immunodominant and evolutionary conserved with homologs present in mammalian cells. Microbial HSP are now known to induce Tregs that crossrecognize mammalian HSP. In addition, microbial exposures, both friendly and nonfriendly, cause cell stress and, consequently, HSP upregulation in host cells. Also such upregulated HSP can activate HSP-specific Tregs that target the upregulated HSP at sites of inflammatory stress wherever in our body. Under inflammatory conditions, cell stress-associated HSP are abundant and therefore easy targets for cognate T-cell interactions. Herewith, they provide a molecular basis for the hygiene hypothesis.

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IL-10 Is Critically Involved in Mycobacterial HSP70 Induced Suppression of Proteoglycan-Induced Arthritis

Cited by 57 publications

References 39 publications

Heat Shock Protein 70: Roles in Multiple Sclerosis

Heat Shock Protein 70: Roles in Multiple Sclerosis

T cell recognition of naturally presented epitopes of self-heat shock protein 70

Immune Recognition of Heat Shock Proteins Provides a Molecular Basis for the “Hygiene Hypothesis” Linking High Prevalence of Immune Disorders to Lack of Cell Stress Eliciting Events

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