Research Topic

The immunology of cellular stress proteins

About this Research Topic

Stress proteins or heat-shock proteins (HSP) are evolutionary conserved proteins present in every prokaryotic and eukaryotic cell. Their main function is to protect cells and proteins from damage under stressful circumstances. The latter circumstances do include the cell and protein damaging effects of ...

Stress proteins or heat-shock proteins (HSP) are evolutionary conserved proteins present in every prokaryotic and eukaryotic cell. Their main function is to protect cells and proteins from damage under stressful circumstances. The latter circumstances do include the cell and protein damaging effects of inflammation.
The discovery of mycobacterial HSP60 being a critical antigen in the model of adjuvant arthritis, has led to studies that showed the immuno-dominance of microbial HSP60 and the potential of the microbial HSP induced repertoire of antibodies and T cells to cross-recognize the self-HSP homologues of stressed cells. Since then, the research in the immunology of stress proteins started to comprise a widening spectrum of topics with potential medical relevance. Interestingly, since stress proteins have their activities in both innate and adaptive immunity, they are key elements in the cross-roads between both arms of the immune system.

Stress proteins or HSP can be considered as functional 'biomarkers' of inflammation. They are up-regulated locally during inflammation and interestingly, they seem to function as targets for anti-inflammatory regulatory T cells. In experimental models of autoimmunity, mainly arthritis, administration of HSP peptides have been shown to suppress disease. First clinical trials have shown the anti-inflammatory nature of T cell responses to Hsp. In type I diabetes and in rheumatoid arthritis, parenteral and oral administration of Hsp peptides were shown to induce a bias in pro-inflammatory T cells, switching them in the direction of regulatory cytokine production (IL4, IL5 and IL10). In addition a raised level of a marker of natural T regulatory cells, the transcription factor FoxP3, was noted in the RA trial. Other inflammatory diseases or diseases with inflammatory components which feature the immune imprint of the up-regulated Hsp are atherosclerosis, inflammatory bowel diseases, multiple sclerosis and atopic diseases such atopic dermatitis and allergic asthma.

Autoimmune diseases or inflammatory diseases are frequently present in aged individuals. The capacity of cells to develop a stress response declines with age and up-regulation of heat shock proteins is diminished in the aged individual.
The exact role of stress protein specific antibodies in inflammatory diseases is unknown. Whether they are mere biomarkers of inflammation or contribute in the disease process remains to be sorted out. The same is true for soluble stress proteins present in the circulation of individuals with atherosclerosis and other inflammatory conditions.
Tumour associated stress proteins seem to qualify as prognostic biomarkers in many tumours. This may be caused by their activity as cellular stress-resistance enhancers. In addition, it may relate to the cell biology of metastasis or to their functions as targets of regulatory T cells. Despite the lack of membrane anchor sequences in heat shock proteins, there is ample evidence for cell surface expressed members of stress proteins. In the case of tumours they may then function as targets for NK cells. Interestingly, also in prokaryotic species cell surface expression of stress proteins has been documented.
A controversy in the area has arisen concerning claims of stress proteins as danger molecules that have the innate quality of inducing inflammatory responses in dendritic cells or other antigen presenting cells. Apart from the possible contribution of contaminating LPS present in earlier recombinant Hsp preparations, there is good evidence that cells may perceive stress proteins as danger molecules, indeed. The mechanisms involved in these stress proteins activities are ready to be sorted out, amongst others motivated by findings that show additional potential of stress proteins as carriers for prote


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Recent Articles

Loading..

About Frontiers Research Topics

With their unique mixes of varied contributions from Original Research to Review Articles, Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author.

Topic Editors

Loading..

Submission Deadlines

Submission closed.

Participating Journals

Loading..

Topic Editors

Loading..

Submission Deadlines

Submission closed.

Participating Journals

Loading..
Loading..

total views article views article downloads topic views

}
 
Top countries
Top referring sites
Loading..

Comments

Loading..

Add a comment

Add comment
Back to top