Semaphorin 7A initiates T-cell-mediated inflammatory responses through a1b1 integrin (Nature, 2007, 446:680-684)

報告日期: 2007/10/09
報告時間: 17:10/18:00
報告學生: 許家豪
講評老師: 陳舜華

Semaphorin 7A initiates T-cell-mediated

inflammatory responses through a1b1 integrin

Nature 2007 Apr 5; 446(7136): 680-4


Speaker: Jia-Hau Shiu (許家豪)

Commentator: Professor Shun-Hua Chen (陳舜華)

Date: 10/09/07

Time: 17:10~18:00

Place: Room 602




    Semaphorins constitute a large family of soluble and membrane-bound proteins and were first identified owing to their contribution to repulsive axon guidance during development. Semaphorin7A (Sema7A), the only GPI (glycosylphosphatidylinositol)-linked protein in semaphorin family, is expressed by a variety of lymphoid and myeloid cells and by several pre- and postnatal neuronal populations. Sema7A can induce monocyte chemotaxis and cytokine production and is expressed in activated lymphocytes and thymocytes, suggesting an immune function for this molecule. However, the detailed function of Sema7A in the immune system is still unclear. Therefore, authors used cell adhesion assay and knockout mice to investigate the role of Sema7A in immune response. They showed that Sema7A binds and stimulates monocytes through a1b1 integrin. They also found that Sema7A in T cells is recruited to the immunological synapse along with lipid rafts and induces redistribution of a1b1 integrin in macrophages. In the study of inflammatory response, Sema7A/- mice are impaired in their ability to develop experimental autoimmune encephalomyelitis (EAE) and contact hypersensitivity(CHS), but antigen-specific priming of T cells and generation of cytokine-producing effector T cells are not impaired in Sema7A/ mice. Sema7A/ T cells also fail to induce contact hypersensitivity even when they directly injected into the antigen-challenged sites. Thus, Sema7A on antigen-primed T cells is required for the effector function of these cells in enhancing inflammation. Their findings not only demonstrated that Sema7A is an effector molecule in T-cell-mediated inflammation but also revealed a mechanism of integrin-mediated immune regulation. The interaction between Sema7A and a1b1 integrin is a potential therapeutic target for some immune disorders which involve in the effector phases of aberrant inflammatory reactions.



1.      Czopik et al., (2006) Semaphorin 7A is a negative regulator of T cell responses. Immunity, 24, 591-600.

2.      Pasterkamp et al., (2003) Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature, 424, 398-405.