Dysregulated expression of the T cell cytokine Eta-1 in CD4-8- lymphocytes during the development of murine autoimmune disease.

Abstract

SummaryThe development of autoimmune disease in the MRL/MpJ-Ipr inbred mouse strain depends upon the maturation of a subset of T lymphocytes that may cause sustained activation of immunological effector cells such as B cells and macrophages. We tested the hypothesis that abnormal effector cell activation reflects constitutive overexpression of a T cell cytokine. We found that a newly defined T cell cytokine, Eta-1, is expressed at very high levels in T cells from MRLA mice but not normal mouse strains and in a CD4 -8 -45R+ T cell clone. The Eta-1 gene encodes a secreted protein that binds specifically to macrophages, possibly via a cell adhesion receptor, resulting in alterations in the mobility and activation state of this cell type (Patarca, R ., G .

Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice

“…Prior to this study, the Opn product, termed the early T lymphocyte activation 1 (Eta-1) or secreted phosphoprotein 1 (Spp1), had been known for its cytokine activities affecting migration of macrophages to an inflammatory site [14] and polyclonal B cell activation and differentiation [10,15]. With respect to autoimmune disease, Patarca et al [16] reported dysregulated expression of Eta-1 in a T lymphocyte subset (CD4 -CD8 -) during the development of autoimmune disease in MRL/lpr mice. We reported an extensive coding polymorphism of Opn between MRL/ lpr and C3H/lpr mice [9].…”

“…Further studies using MRL/lprOpn C3H/C3H or MRL/lpr-Opn -/-mice should be performed. In autoimmune disease-prone MRL/lpr mice, the level of OPN in serum was found to be increased in association with the onset of autoimmune diseases and expansion of CD3 + /CD4 -/CD8 -T-cells which express OPN mRNA [16]. Several studies have demonstrated the link between OPN overexpression and autoimmune diseases including lupus nephritis [28,29], interstitial nephritis [30], rheumatoid arthritis [31] and pulmonary fibrosis [32].…”

Osteopontin, a Coordinator of Host Defense System: a Cytokine or an Extracellular Adhesive Protein?

“…OPN is also secreted into various body fluids, including milk, serum, urine and cochlear fluid. OPN is very unique in the sense that it can be classified not only as extracellular matrix but also a lymphokine since it possesses a signal sequence and is secreted by activated T cells and regulates various immune functions (25,32,38,39,48 OPN and Immune System OPN was also identified as early T lymphocyte activation-1 (Eta-1). An Eta-1 cDNA was strongly expressed after activation of T cells.…”

SIBLING Expression Patterns in Duct Epithelia Reflect the Degree of Metabolic Activity

“…However, some earlier reports indicated the expression of OPN in human breast milk (Senger et al 1989), chronic inflammatory cells (Patarca et al 1990), and kidney (Shiraga et al 1992), as well as some other epithelia (Brown et al 1992). Terasawa et al (2004) have also reported expression of DMP1 in several mouse soft tissues including liver, muscle, brain, pancreas, and kidney, by immunohistochemistry (IHC) and RT-PCR.…”