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T-Cell Immunoglobulin and Mucin Domain Containing 4 (TIM4)

The T-cell Ig mucin (TIM) family of genes encodes proteins that are expressed by T cells and contain an IgV-like and a mucin-like domain. The TIM family consists of three genes in human (TIM-1, TIM-3, and TIM-4). TIM-4 is a phosphatidylserine (PS) receptor expressed in mature antigen presenting cells that enhances phagocytosing activity of apoptotic cells by macrophages to maintain the homeostasis. TIM-4 plays an essential role in controlling of adaptive immunity by regulating the clearance of antigen-specific cells. Mice lack of TIM-4 causes failure to clean apoptotic bodies in vivo, leading to dysregulated lymphocyte activation and signs of systemic autoimmunity, implying that TIM-4 may be associated with the susceptibility to allergic and autoimmune diseases. The role of TIM-4 in regulating immune responses was investigated in several other models. Several studies suggest that TIM-4 may play a role in maintaining oral tolerance and prevention of food allergy. TIM-4 is expressed by macrophages and dendritic cells in human tissue, we examined its expression in a range of histiocytic and dendritic cell neoplasms and found moderate to strong immunohistochemical staining in cases of juvenile xanthogranuloma and histiocytic sarcoma, and lower level staining in interdigitating dendritic cell sarcoma, Langerhans cell histiocytosis, acute monocytic leukemia (leukemia cutis), and blastic plasmacytoid dendritic cell neoplasm (hematodermic tumor). TIM-4, is expressed in a range of histiocytic and dendritic cell neoplasms, typically with strong immunohistochemical staining. TIM-4 fusion protein induce an increase of T cells proliferation but in lower concentration it inhibited T cells response. Other findings show that in vivo administration of TIM-4 antibody apparently induced TH1 cells proliferation and that TIM-4 fusion protein is able to induce an increase of interferon gamma (IFN-g) and tumor necrosis factor-alpha (TNF-a) rate in vitro.

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