Signaling and Cell Biology of TIM-1

描述（由申请人提供）：跨膜免疫球蛋白和粘蛋白（TIM）家族的蛋白质与小鼠和人类的多种功能有关。该家族的创始成员TIM-1最初被描述为甲型肝炎病毒（HAVcr-1）的受体。最初对TIM-1在免疫中的可能作用的兴趣主要集中在T细胞上

DESCRIPTION (provided by applicant): Proteins of the transmembrane immunoglobulin and mucin (TIM) family have been linked to a wide variety of functions in mice and humans. The founding member of the family, TIM-1, was first described as a receptor for the hepatitis A virus (HAVcr-1). Initial interest in the possible role of TIM-1 in immunity focused on T cells, due to an association between TIM-1 polymorphisms and commitment of helper T cells to either the Th1 or Th2 lineage. More recent studies have greatly broadened the possible role of TIM-1 in the immune system, including implicating this protein in the regulation of mast cells, which are also intimately involved in atopic disease. Our approach to understanding the function of TIM-1 has been to focus mainly on the signaling pathways downstream of this protein, as well as its cell biology. We believe that this approach is an important complement to the in vivo studies of others, which have yet to yield a consistent story regarding TIM-1 function in mouse models of atopic disease. Our recent studies have begun to reveal interesting biology associated with the function of TIM-1 in T cells. In this renewal application, we will continue our efforts to define te function of TIM-1 on T cells, but also broaden our studies to include investigation of the role of this protein in mast cells, both in vitro and in vivo. We believe that the studies outlined in this proposal have great potential to aid in the understanding of the effects of in vivo modulation of TIM-1, which has shown potential in pre-clinical models of asthma.