Disease relevance of VSIG4

• Z39Ig staining in the osteoarthritis synovium was restricted to macrophages in the lining layers [1].

High impact information on VSIG4

• The specific expression of VSIG4 on resting macrophages in tissue suggests that this inhibitory ligand may be important for the maintenance of T cell unresponsiveness in healthy tissues [2].
• In this issue of the JCI, Vogt et al. show that the B7 family-related protein V-set and Ig domain-containing 4 (VSIG4) can act as an inhibitor of T cell activation (see the related article beginning on page 2817) [3].
• Z39Ig staining was also observed in macrophages in the lining layers and sublining areas of rheumatoid arthritis synovium [1].
• To identify the role(s) of Z39Ig in the function of macrophages, we used human monocytic cell lines TF-1A (Z39Ig-negative) and THP-1 (Z39Ig-positive) [1].
• Z39Ig, a recently identified immunoglobulin (Ig) superfamily member, is localized in the pericentromeric region of human chromosome X and detectable in all human tissue, but it is predominantly expressed in fetal human tissues as well as in adult lungs and placenta [4].

Biological context of VSIG4

• Cloning of Z39Ig, a novel gene with immunoglobulin-like domains located on human chromosome X [5].
• The sequence and expression data suggest that Z39Ig is a cell surface receptor, expressed in activated macrophages, and linked with the classical complement system, most likely in phagocytosis preceding antigen presentation [6].
• We examined expression of Z39Ig in 1432 human cDNA libraries, and found it primarily in synovium of patients with rheumatoid arthritis, in placenta, and in lung [6].
• These data suggest that the Z39Ig protein might be a critical molecule to regulate an immune response mediated by phagocytosis and/or antigen presentation [4].

Anatomical context of VSIG4

• Abundant expression of transcripts was detected in several human fetal tissues, whereas among adult tissues lung and placenta express highest levels of Z39Ig mRNA [5].
• The anti-Z39Ig mAb that we generated specifically bound to Z39Ig protein on human promonocytic THP-1 cells, monocytes isolated from human peripheral blood mononuclear cells (PBMC) and mature CD14(+) dendritic cells (DC) differentiated from umbilical-cord blood CD34(+) hematopoietic progenitor cells [4].

References