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T-cell immunoglobulin and mucin domain-containing protein 2 (TIM-2) is a type I transmembrane glycoprotein and a member of the TIM family of immunoregulatory proteins. In mice, TIM-2 is expressed on activated T cells (specifically Th2 cells), B cells (especially in germinal centers), and in non-hematopoietic tissues such as the liver, kidney, and brain (oligodendrocytes). It serves as a receptor for H-ferritin, mediating its endocytosis and contributing to cellular iron homeostasis, and also interacts with Semaphorin 4A (Sema4A) to regulate T-cell activation and Th2 cytokine production. While TIM-2 plays a significant role in murine models of autoimmunity (e.g., experimental autoimmune encephalomyelitis) and allergy, it is not expressed in humans, where the TIMD2 gene is a pseudogene. Consequently, TIM-2 is primarily a target for preclinical research and mechanistic studies rather than a direct human therapeutic target, although its functional roles are often compared to those of human TIM-1.
Blockade of TIM-2/ligand interaction (e.g., Sema4A or H-ferritin) to modulate Th2-mediated immune responses or cellular iron uptake.
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