Department of Immunopathology

Research Group / Research Projects / Major publications /

Research Group

Research Projects

Regulation of immune responses by "Immune Semaphorins"

The semaphorin family contains soluble and membrane-bound proteins that were first identified as axonal guidance cues that function during neuronal development. However, cumulative findings suggest that semaphorins also play diverse roles in processes that are unrelated to axon guidance, including organogenesis, vascularization, angiogenesis, apoptosis and neoplastic transformation. After we discovered that CD100/Sema4D participates in the immune system, we have found that a subset of semaphorins called the 'Immune Semaphorins' also function in the immune system. These include Sema4A, CD100/Sema4D, Sema6D, and Sema7A. In addition, we found recently that Sema3A plays an essential role in the migration of dendritic cells (Fig. 2). We are currently studying the molecular mechanisms by which semaphorins and their receptors regulate immune responses.

Fig.1

Figure 1. Representative immune semaphorins. The involvement of these semaphorins in immune responses has been demonstrated by using gene-targeted mice.

Fig.2

Figure 2. Sema3A is important in the migration of DCs.


Major publications

  1. Okuno T, Nakatsuji Y, Moriya M, Takamatsu H, Nojima S, Takegahara N, Toyofuku T, Nakagawa Y, Kang S, Friedel RH, Sakoda S, Kikutani H, Kumanogoh A.¡¡Roles of Sema4D-plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis.¡¡J Immunol. 2010 Feb 1;184(3):1499-506.
  2. Toyofuku T, Yoshida J, Sugimoto T, Yamamoto M, Makino N, Takamatsu H, Takegahara N, Suto F, Hori M, Fujisawa H, Kumanogoh A, Kikutani H.¡¡ Repulsive and attractive semaphorins cooperate to direct the navigation of cardiac neural crest cells. Dev Biol. 2008 Sep 1;321(1):251-62.
  3. Suzuki K, Kumanogoh A, Kikutani H. Semaphorins and their receptors in immune cell interactions. Nat Immunol. 2008 Jan;9(1):17-23.
  4. Suzuki K, Okuno T, Yamamoto M, Pasterkamp J, Takegahara N, Takamatsu H, Kitao T, Takagi J, Rennert P, Kolodkin A, Kumanogoh A, Kikutani H. Semaphorin 7A initiates T-cell mediated inflammatory responses through¦Á1¦Â1 intergrin. Nature 2007 Apr 5;446(7136):680-4.
  5. Takegahara N, Takamatsu H, Toyofuku T, Tsujimura T, Okuno T, Yukawa K, Mizui M, Yamamoto M, Prasad DV, Suzuki K, Ishii M, Terai K, Moriya M, Nakatsuji Y, Sakoda S, Sato S, Akira S, Takeda K, Inui M, Takai T, Ikawa M, Okabe M, Kumanogoh A, Kikutani H. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat Cell Biol. 2006 Jun;8(6):615-22.
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