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Heat Shock Proteins and Alarmins in Autoimmunity

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Heat Shock Proteins in Signaling Pathways

Part of the book series: Heat Shock Proteins ((HESP,volume 17))

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Abstract

Autoimmunity represents a diverse group of diseases, which demonstrate complex immuno-pathological responses. Heat shock proteins (Hsp) and danger signaling proteins such as HMGB1 and RAGE, grouped as alarmins play a crucial role in autoimmunity. These proteins are present at elevated levels in the patient’s plasma. Hsp bind and stabilize large protein complexes such as immune complexes (ICs), which are formed with autoantibodies generated against modified proteins and nucleic acids that are released from apoptotic and dead cells. Alarmins protect nucleic acids from degrading and enhance ICs capability to produce proinflammatory cytokines. Our current understanding of the role of Hsp in disease is largely based on the studies performed in innate immune cells. In autoimmunity, CD4+ T cells are a major contributor of pathology in inflamed tissue. Activation of CD4+ T cells by ICs triggers upregulation of a large set of genes that encode Hsp and also the HMGB1. HMGB1 associates with the low affinity Fc receptor, which trigger the release of proinflammatory cytokines from ICs ligation. This chapter will address our current understanding of the role and interplay of Hsp with other alarmins in autoimmune pathology. Additionally, it will also address the possible role of low affinity Fc receptors in triggering Hsp and alarmins mediated responses in autoimmune pathology.

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Abbreviations

17-AAG:

allyamino-17-dimethoxygeldamycin

APC:

antigen presenting cells

BCR:

B cell receptor

CpG:

cytosine-phosphate- guanine

DAMPs:

damage-associated molecular patterns

DC:

dendrocyte

ER:

endoplasmic reticulum

Grp-78:

glucose-regulated protein 78

HMGB1:

high mobility group box 1

Hsp:

heat shock proteins

HSPB1:

heat shock protein family B member 1

ICs:

immune complexes

IFNs:

interferons

JIA:

juvenile idiopathic arthritis

LPS:

lipopolysaccharides

MAP:

mitogen activated protein kinase

MMP:

matrix metalloproteinase

PAMPs:

pathogen-associated molecular patterns

pDCs:

plasmacytoid dendritic cells

PRRs:

pattern recognition receptors

PS:

phosphotidyl serine

RA:

rheumatoid arthritis

RAGE:

receptor for advanced glycation end-products

SLE:

systemic lupus erythematosus

TCR:

T cell receptor

TE :

effector T cells

TLRs:

toll-like receptors

TRAF-6:

TNF receptor associated

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Acknowledgements

This work was supported by National Institute of Health Grant RO1 A1098114.

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Authors and Affiliations

  1. Division of Adult and Pediatric Rheumatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA

    Anil K. Chauhan

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Correspondence to Anil K. Chauhan .

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Editors and Affiliations

  1. Professor, Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center Eleanor N. Dana Cancer Center, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Chauhan, A.K. (2019). Heat Shock Proteins and Alarmins in Autoimmunity. In: Asea, A., Kaur, P. (eds) Heat Shock Proteins in Signaling Pathways. Heat Shock Proteins, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-030-03952-3_7

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