Sema4A and Chronic Inflammation

Abstract

Semaphorins were originally identified as axon guidance factors involved in the development of the nervous system. However, accumulating evidence indicates that several semaphorins, so-called 'immune semaphorins', have important functions in various phases of pathological and physiological immune responses, such as cell-cell interactions, immune-cell activation, differentiation, and trafficking/migration. For example, Sema4A, a class IV transmembrane semaphorin, plays crucial roles in dendritic cells, macrophages, and T cells. In addition, Sema4A is involved in various chronic inflammatory diseases including multiple sclerosis, asthma/allergic rhinitis/ atopic dermatitis, and retinitis pigmentosa. Keywords Semaphorin • Sema4A • Multiple sclerosis • Asthma/allergic rhinitis/ atopic dermatitis • Retinitis pigmentosa 3.1 Introduction Semaphorins, which are secretory and/or membrane proteins characterised by a conserved amino-terminal Sema domain, were originally identified as repulsive axon-guidance factors involved in neuronal development (Kolodkin et al. 1993; Tamagnone and Comoglio 2000; Pasterkamp and Kolodkin 2003). Vertebrate semaphorins, including immune semaphorins, are classified into classes III-VII, and invertebrate semaphorins are grouped into classes I and II. Semaphorins exert pleiotropic functions, playing roles in cardiogenesis (Toyofuku and Kikutani 2007; Toyofuku et al.