Journal Article

Hsp70 Regulates Immune Response in Experimental Autoimmune Encephalomyelitis

Costa, Carme, Martin, Roland, Aigrot, Marie-Stéphane, Tepavcevic, Vanja, Lubetzki, Catherine, Mansilla, M. José, Montalban, Xavier, Espejo, Carmen, Castillo, Mireia, Eixarch, Herena

2014

Overview

Heat shock protein (Hsp)70 is one of the most important stress-inducible proteins. Intracellular Hsp70 not only mediates chaperone-cytoprotective functions but can also block multiple steps in the apoptosis pathway. In addition, Hsp70 is actively released into the extracellular milieu, thereby promoting innate and adaptive immune responses. Thus, Hsp70 may be a critical molecule in multiple sclerosis (MS) pathogenesis and a potential target in this disease due to its immunological and cytoprotective functions. To investigate the role of Hsp70 in MS pathogenesis, we examined its immune and cytoprotective roles using both in vitro and in vivo experimental procedures. We found that Hsp70.1-deficient mice were more resistant to developing experimental autoimmune encephalomyelitis (EAE) compared with their wild-type (WT) littermates, suggesting that Hsp70.1 plays a critical role in promoting an effective myelin oligodendrocyte glycoprotein (MOG)-specific T cell response. Conversely, Hsp70.1-deficient mice that developed EAE showed an increased level of autoreactive T cells to achieve the same production of cytokines compared with the WT mice. Although a neuroprotective role of HSP70 has been suggested, Hsp70.1-deficient mice that developed EAE did not exhibit increased demyelination compared with the control mice. Accordingly, Hsp70 deficiency did not influence the vulnerability to apoptosis of oligodendrocyte precursor cells (OPCs) in culture. Thus, the immunological role of Hsp70 may be relevant in EAE, and specific therapies down-regulating Hsp70 expression may be a promising approach to reduce the early autoimmune response in MS patients.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptive immunity / Animals / Antigens / Apoptosis / Autoimmunity - immunology / Biology and Life Sciences / Cell culture / Cell Proliferation / Cytokines / Demyelination / Encephalomyelitis, Autoimmune, Experimental - immunology / Encephalomyelitis, Autoimmune, Experimental - metabolism / Experimental allergic encephalomyelitis / Gene expression / Glial stem cells / Glycoproteins / Heat shock proteins / HSP70 Heat-Shock Proteins - genetics / HSP70 Heat-Shock Proteins - metabolism / Hsp70 protein / Immune response / Immune system / Immunology / Life Sciences / Lymphocytes / Lymphocytes T / Medicine and Health Sciences / Mice / Mice, Knockout / Microglia - immunology / Microglia - metabolism / Multiple sclerosis / Myelin / Myelin Proteins - metabolism / Myelin-Oligodendrocyte Glycoprotein - metabolism / Neurobiology / Neurons and Cognition / Neuroprotection / Oligodendrocyte-myelin glycoprotein / Pathogenesis / Proteins / Research and Analysis Methods / Rodents / Stress / T-Lymphocytes - immunology / T-Lymphocytes - metabolism