T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) and T-cell immunoglobulin and mucin domain-containing protein 4 (TIM4) (TIM3 (for T-cell immunoglobulin and mucin domain-containing protein 3), TIM4 (for T-cell immunoglobulin and mucin domain-containing protein 4))

T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) and protein 4 (TIM4) are members of the TIM family of immune regulatory molecules that play major roles in modulating innate and adaptive immunity. TIM3 is expressed on exhausted T cells, dendritic cells, and myeloid cells, where it functions as a major immune checkpoint, negatively regulating immune responses and contributing to tumor immune evasion as well as immune exhaustion in chronic infection and cancer[1][5][6]. TIM3 binds ligands such as galectin-9 and phosphatidylserine and is a key therapeutic target in immuno-oncology. TIM4 is a phosphatidylserine receptor expressed mainly on antigen-presenting cells such as macrophages and dendritic cells[2][4][5][7]. It mediates the uptake and clearance of apoptotic cells (efferocytosis), thus promoting immune tolerance and maintaining tissue homeostasis. TIM4 also interacts with TIM1 on T cells, modulating T cell activation, proliferation, and apoptosis[3][7]. Both receptors are implicated in immune-related diseases, including cancer, chronic inflammatory conditions, and infections, and are under investigation as therapeutic targets for modulating immune responses.

Other names

TIM-3 (HAVCR2)TIM-4 (TIMD4)T cell immunoglobulin and mucin domain 3/4Hepatitis A virus cellular receptor 2 (for TIM-3)T cell membrane protein 3/4

Immune checkpoint inhibition (anti-TIM3 drugs); Augmentation of T cell and innate immune responses (anti-TIM3); Reversal of T cell exhaustion (anti-TIM3); Modulation of immune tolerance (theoretical for TIM4 targeting)[7]; Blockade of phosphatidylserine binding (for both by experimental antibodies)