First published online July 31, 2003
Journal of Cell Science 116, e1701 (2003)
Copyright © 2003 The Company of Biologists Limited
Signalling in semaphore - from dendrite to dendritic cell
The semaphorins are a family of proteins that have well-established roles
as axon guidance cues in the developing nervous system. Certain semaphorins
might have additional functions, however - for instance, in angiogenesis,
organogenesis and apoptosis. In a Commentary on
p. 3463, Atsushi
Kumanogoh and Hitoshi Kikutani discuss recent work indicating that some
members of this family function in the immune system. The class IV semaphorin
Sema4D, for example, is expressed on T cells and implicated in activation of B
cells and dendritic cells. Sema4A, by contrast, is expressed on B cells and
dendritic cells and implicated in activation of T cells. Both are
transmembrane proteins that interact with specific receptors on the target
cell (plexin-B1/CD72 and Tim-2, respectively), but Sema4D can also be
proteolytically released as a soluble ligand. Several viruses have taken
advantage of the immunoregulatory functions of semaphorins by encoding related
molecules that allow them to regulate host immune responses - in the case of
the alcelaphine herpesvirus, it produces a protein similar to Sema7D, which
stimulates inflammatory responses. Given their immunological roles,
semaphorins could, by contrast, be used clinically to combat pathogens. Indeed
recent in vivo studies combining conventional immunization with administration
of Sema4A or Sema4D are encouraging in this respect.
Related articles in JCS:
- Immune semaphorins: a new area of semaphorin research
- Atsushi Kumanogoh and Hitoshi Kikutani
JCS 2003 116: 3463-3470.
[Abstract]
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