title: The role of Sema4D/CD100 as a therapeutic target for tumor microenvironments and for autoimmune, neuroimmune and bone diseases.
abstract: BACKGROUND
  Semaphorin 4D (Sema4D), also known as CD100, has been implicated in physiologic roles in the immune and nervous systems. However, the interaction of Sema4D with its high affinity receptor, Plexin-B1, reveals a novel role for Sema4D produced by the tumor microenvironment in tumor angiogenesis and metastasis.
  
  
  METHODS
  The ligation of Sema4D/CD100 with CD72 on immune and inflammatory cells is known to stimulate immune responses and regulation. Because CD100 and CD72 are expressed on lung immune and nonimmune cells, as well as on mast cells, the CD100/CD72 interaction plays another important role in allergic airway inflammation and mast cell functions. A better understanding of Sema4D-mediated cell signaling in physiological and pathological processes may be crucial for crafting new Sema4D-based therapeutics for human disease and tumor microenvironments. Strategies to achieve effective management through treatment with Sema4D include special siRNAs, neutralizing antibodies and knockdown.
  
  
  CONCLUSIONS
  This review focuses on the links between Sema4D and human diseases such as cancer, bone metabolism, immune responses and organ development. The current knowledge regarding the expression of Sema4D and its receptors and its functional roles is systemically reviewed to explore Sema4D as both a target and a therapeutic in human diseases.
authors.affiliation: a Cancer Biology Research Center, Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wu
authors.affiliation: a Cancer Biology Research Center, Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: a Cancer Biology Research Center, Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Gao
authors.affiliation: b Department of Neurosurgery, Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D001847:Bone Diseases / Q000276:immunology / Q000628:therapy; D055785:Gene Knockdown Techniques; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy; D015213:Neuroimmunomodulation / Q000276:immunology; D039961:Semaphorins / Q000008:administration & dosage / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D039961:Semaphorins
keywords: Sema4D; bone diseases; neuroimmune; plexinB1; tumor microenvironments