Exogenous truncated IK protein ameliorates inflammatory arthritis.

Abstract

The truncated IK (tIK) cytokine is known for its ability to downregulate the major histocompatibility complex class II on antigen-presenting cells and to regulate immune activation in inflammatory diseases by suppressing differentiation of pathogenic T cells and activation of macrophage. Because of these immune regulatory functions, previous research has proposed tIK as a new candidate for autoimmune disease therapy such as that for rheumatoid arthritis (RA). However, its immunological mechanism is still not identified clearly. In this study, we showed that exogenous tIK protein produced by the insect expression system suppressed the differentiation of TH1 and TH17 cells, which are key factors of inflammatory arthritis. We also showed that tIK protein reduced symptoms of the disease in the collagen antibody-induced arthritis (CAIA) mouse model. In addition, to investigate the receptor and signal transducers that directly interact with tIK and/or the intracellular molecules as a signal pathway, we performed a protein–protein interaction array. According to protein array data, FAM104B, CUTA, GSN, YEATS4 and some other proteins might interact with tIK protein. Among them some proteins may serve as the negative regulators of NF-kappaB transcription factor. Therefore, we suggest that tIK protein has the potential to act as a new therapeutic agent for RA patients, because it has a different mode of action compared with the currently-used biologics for RA, such as monoclonal antibody drugs.