T-cell immunoglobulin and mucin domain-containing protein 4 (TIM-4) (TIM-4)

T-cell immunoglobulin and mucin domain-containing protein 4 (TIM-4) is a cell surface receptor primarily expressed on professional antigen-presenting cells, including macrophages and dendritic cells (UniProt: Q6U7R4). It serves as a critical receptor for phosphatidylserine, a phospholipid that is translocated to the outer leaflet of the plasma membrane during apoptosis, thereby facilitating the recognition and engulfment of dying cells, a process known as efferocytosis (PubMed: 17850460). While TIM-4 lacks a classical intracellular signaling domain, it plays a significant role in modulating immune responses and maintaining peripheral tolerance. In oncology, TIM-4 is often exploited by the tumor microenvironment; its expression on tumor-associated macrophages can lead to the suppression of anti-tumor T-cell activity (PubMed: 23602551). Experimental therapeutic approaches utilize anti-TIM-4 monoclonal antibodies to block the interaction between TIM-4 and phosphatidylserine, aiming to promote a more pro-inflammatory environment and enhance the efficacy of cancer vaccines and other immunotherapies. Additionally, TIM-4 has been implicated in the pathogenesis of allergic diseases and various autoimmune conditions due to its role in regulating Th2 cell expansion.

Other names

Timd4TIM4SMUCKLERSpleen, mucin-containing, knockout of lymph node receptor

Antagonism of phosphatidylserine binding to prevent efferocytosis-mediated immunosuppression and enhance T-cell activation.