TIM-1 regulates macrophage cytokine production and B7 family member expression.

T-cell immunoglobulin mucin-1 (TIM-1) is associated with the regulation of T helper type 2 (Th2) immune responses and has been associated with asthma susceptibility. Previous studies have shown that administration of TIM-1 results in T cell hyperproliferation and increased Th2 cytokine secretion. TIM-1 has also been shown to bind to macrophages, but the effects of TIM-1 administration on macrophage activity have not been assessed. In this study we demonstrate that TIM-1 binds to the mouse macrophage cell line RAW 264.7. Stimulation of the RAW264.7 cells with TIM-1 increases nitric oxide production. A dramatic increase in the pro-inflammatory cytokines TNF-alpha and IL-6 is seen upon TIM-1 stimulation of RAW 264.7 cells. Additionally, there is a moderate increase in the immuno-modulatory cytokine IL-10 when RAW 264.7 cells are stimulated with TIM-1. TIM-1 stimulation also alters the expression of some members of the B7 family of co-stimulatory/co-inhibitory proteins. TIM-1 stimulation leads to increased B7-1, B7-H1, and PD-L2 expression, while inhibiting B7-H2 expression. These studies suggest that TIM-1 can regulate macrophage activation and alter the co-stimulatory properties of macrophages and thus may contribute to allergic inflammatory diseases such as asthma.