Regulation of T-helper-cell lineage development by osteopontin: the inside story

Abstract

Here, Harvey Cantor and Mari Shinohara propose that the secreted and intracellular isoforms of osteopontin differentially regulate the development of distinct T-helper-cell subsets and, consequently, adaptive immune responses to foreign and self antigens. Studies of osteopontin (OPN)-dependent regulation of immune responses have focused on the cytokine activities of the secreted form of this protein. Recent evidence has revealed that an intracellular form of OPN expressed by dendritic cells regulates the expression of pro-inflammatory cytokines and the differentiation of T helper (TH)-cell lineages. In this Opinion article, we discuss the properties of both OPN isoforms and their respective contributions to the immune response. We propose that cell-type-specific expression of secreted and intracellular OPN regulates the development of distinct effector TH cells, including that of TH1 and TH17 cells.