Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity

Abstract

Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. Mice deficient in Eta-1 (also called osteopontin) gene expression have severely impaired type-1 immunity to viral infection [herpes simplex virus-type 1 (KOS strain)] and bacterial infection (Listeria monocytogenes) and do not develop sarcoid-type granulomas. Interleukin-12 (IL-12) and interferon-gamma production is diminished, and IL-10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.

Osteopontin: Role in immune regulation and stress responses

“…(Rollo et al, 2005). Likewise, OPN-deficient mice are impaired in their ability to clear L. monocytogenes after systemic infection (Ashkar et al, 2000). Fig.…”

“…The ligation of OPN and CD44 variants mediates chemotaxis and adhesion of fibroblasts, T cells and bone marrow cells (Weber et al, 1996;Wai and Kuo, 2004). CD44 engagement with OPN down-regulates IL-10 expression in peritoneal macrophages (Ashkar et al, 2000). Furthermore, OPN promotes proliferation and survival of IL-3-dependent bone marrow cells; anti-CD44 antibody attenuates these effects (Lin et al, 2000).…”

“…At sites of tissue injury, OPN produced by macrophages fosters cell adhesion and may act as an opsonin facilitating phagocytosis of foreign bodies (McKee and Nanci, 1996). It has been demonstrated that, in macrophages, a phosphorylation-dependent interaction between the amino-terminal portion of OPN and its integrin receptor stimulated IL-12 expression, whereas a phosphorylationindependent interaction with CD44 inhibited IL-10 expression (Ashkar et al, 2000).…”

“…This concept is emphasized by the deficiency of Th1 immunity in OPN-deficient mice, which leads to a compromised host defense against bacterial and viral infections (Rollo et al, 2005, Koguchi et al, 2002 and ameliorated autoimmunity (Chabas et al, 2001). with the α v β 3 integrin to induce pro-inflammatory IL-12 and 2) ligation of CD44v to suppress anti-inflammatory cytokine IL-10 production (Ashkar et al, 2000). Autocrine amplification of cytokine production and cross-inhibition ensure progressive polarization of the T-helper cells towards either Th1 or Th2 cells (Abbas et al, 1996).…”

“…OPN has been identified as a major factor in the regulation of immune responses and inflammation; its expression is up-regulated in activated T cells, macrophages and NK cells Shinohara et al, 2005). It is classified as a Th1 cytokine because it enhances production of the Th1 cytokines IFN-γ and IL-12 and inhibits production of the Th2 cytokine IL-10 by macrophages (Ashkar et al, 2000;Renkl et al, 2005). The roles that OPN plays in mammalian systems physiology are diverse.…”