Immunological Properties
Like many stress and heat shock proteins, BiP/GRP78 has potent immunological activity when released from the internal environment of the cell into the extracelluar space. Specifically, it feeds anti-inflammatory and pro-resolutory signals into immune networks, thus helping to resolve inflammation.
The mechanisms underlying BiP's immunological activity are incompletely understood. However, it has been shown that it binds to a receptor on the surface of monocytes and induces anti-inflammatory cytokine secretion dominated by IL-10, IL-1Ra, and sTNFR. Furthermore, it downregulates critical molecules involved in T-lymphocyte activation such as HLA-DR and CD86. It also modulates the differentiation pathway of monocytes into dendritic cells, causing them to develop tolerogenic characteristics, which, in turn, can facilitate the development of regulatory T-lymphocytes.
The potent immunomodulatory activities of BiP/GRP78 have also been demonstrated in animal models of autoimmune disease including collagen-induced arthritis, a murine disease that resembles human rheumatoid arthritis. Prophylactic or therapeutic parenteral delivery of BiP has been shown to ameliorate clinical and histological signs of inflammatory arthritis.
Read more about this topic: Binding Immunoglobulin Protein
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