Neural-Immune Select

Traditionally, the functions of classical immune molecules were thought to be restricted to the immune system. However, accumulating evidence demonstrates that some immune proteins contribute to neuronal function. Building upon these observations, McConnell et al. provide direct evidence for a role of MHCI molecules in cerebellar synaptic plasticity and behavior. The authors found that the classical MHCI molecules H2-K and H2-D are selectively expressed in Purkinje cells and that loss of these proteins led to a lower LTD induction threshold at cerebellar synapses and enhanced motor learning in mice. A recent study by Atwal et al. further expands the role of immune molecules in the nervous system to include the modulation of axonal growth and the regulation of axon regeneration. Three myelin proteins (Nogo, MAG, and OMgP) inhibit axon regeneration. Deletion of their receptor NgR does not fully prevent their inhibitory effects, suggesting that another receptor may be involved. In search of this receptor, the authors discovered that PirB, an MHCI receptor previously implicated in synaptic plasticity, acts as a high-affinity receptor for Nogo, MAG, and OMgP. Blocking both PirB and NgR prevented nearly all of the inhibitory effects of these proteins on axon outgrowth, raising the exciting possibility that targeting the activity of both NgR and PirB in vivo might potentially stimulate axon regeneration. McConnell et al. (2009). PNAS 106, 6784–6789. Atwal et al. (2008). Science 322, 967–970.