T cells set off a multiple sclerosis–like disease in mice, but problems with a myeloid cell brake escalate the damage, according to a report by Xi and colleagues.
Various populations of immune cells invade the CNS during experimental autoimmune encephalomyelitis (EAE), a demyelinating disease in mice. One population—CD11c-expressing myeloid cells—provokes the destruction of myelin sheathes that protect nerves by presenting antigens to infiltrating T cells, and by producing inflammatory cytokines and reactive oxygen intermediates. Whether the latter secretions rely on the T cell response has remained elusive. Now, Xi et al. find that myeloid cells can wreak havoc without the help of T cells. And the destruction is heightened in the absence of a myeloid inhibitory receptor called CLM-1.
CLM-1 was expressed on CD11c-expressing myeloid cells that invaded the spinal cord during disease. Without CLM-1, demyelination and disease worsened rapidly—but not because the myeloid cells were more adept at activating disease-inducing T cells. In fact, the receptor inhibited CNS damage only after the disease began.
Whether multiple sclerosis patients bear defects in the human orthologue of CLM-1, CD300f, remains to be seen. If so, CLM-1 and its as-yet-unknown ligand could be manipulated to stifle inflammation in this and other demyelinating diseases.
