T cell immunoglobulin and mucin-domain receptor family and TAM receptor tyrosine kinase family (TIM and TAM receptor families)

The **TIM-family receptors** (T cell immunoglobulin and mucin-domain containing molecules: TIM-1, TIM-3, and TIM-4 in humans) are type I cell membrane proteins characterized by an immunoglobulin variable domain and a mucin domain[3][5]. They mediate regulatory functions in adaptive and innate immunity, including inhibiting or stimulating the activity, survival, and differentiation of T cells, B cells, dendritic cells, macrophages, and mast cells[3][5][4]. TIM members play roles in immune homeostasis, tolerance, allergy, and efferocytosis (clearance of apoptotic cells). The **TAM-family receptors** (Tyro3, Axl, Mer receptor tyrosine kinases) are receptor tyrosine kinases critical for regulation of innate immune response, tissue repair, apoptotic cell phagocytosis, and immune homeostasis[1]. Through their ligands Gas6 and Protein S, they act mainly as inhibitors of immune activation and are implicated in the progression of cancer, autoimmune disease, inflammatory disease, and infections[1]. Both TIM and TAM families are considered important therapeutic targets in immuno-oncology and immune regulation, but their overlapping and distinct roles mean each member (e.g., TIM-3, Axl) is usually described as a separate target in clinical and therapeutic contexts.

Other names

TIM family: T cell immunoglobulin and mucin domain-containing moleculesTAM family: Tyro3, Axl, and Mer receptor tyrosine kinasesAlternative gene/protein names for TIM-1: Hepatitis A virus cellular receptor 1 (HAVCR1), Kidney injury molecule 1 (KIM-1)Alternative gene/protein names for TIM-3: HAVCR2Alternative gene/protein names for TIM-4: TIMD4Alternative gene/protein names for TAM receptors: Sky (Tyro3), Ufo (Axl), Mertk (Mer)

TIM family: Blockade of TIM-3 can enhance T cell and innate immune responses by preventing its inhibitory effects. TIM-1-targeting agents can modulate regulatory T/B cell activity. TAM family: Inhibition of TAM kinases (especially Axl, Mer) blocks negative feedback on immune activation, enhances anti-tumor immunity, and reduces efferocytosis. Anti-TAM agents may disrupt tumor cell survival signaling.