Crucial role of TNFα-induced adipose-related protein (TIARP) in the pathogenesis of autoimmune arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a variable disease outcome, and is characterized by inflammation of multiple joints. Proinflammtory cytokines, such as tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6) are thought to play crucial roles in the pathology of RA. The prognosis of patients with RA has improved significantly with the recent availability of biologics targeting TNFα and IL-6. Immunization of DBA/1 mice with glucose-6-phosphate isomerase (GPI) induces severe acute arthritis. This arthritis can be controlled by TNFα antagonists, suggesting similar etiology to RA. We performed GeneChip analysis using splenocytes of mice with GPI-induced arthritis. Among the arrayed TNFα-related genes, the expression of TNFα-induced adipose-related protein (TIARP) mRNA was the highest. TIARP was detected specifically in joints and spleens of arthritic mice. Among the splenocytes, CD11b(+) cells were the main source of TIARP mRNA. STEAP4 (the human ortholog of TIARP) was highly upregulated in joints of patients with RA and especially co-localized with CD68(+) macrophages. In this study, we discuss the role of TIARP in the generation of experimental autoimmune arthritis and the possible clinical application of for the treatment of RA.