Both the pattern of TNFR2 expression and the tight control of TNF RNA expression in the MS brain parenchyma suggest that a TNF-targeting therapeutic strategy for MS should be oriented toward the development of TNFR2 selective agonists rather than TNFR1 antagonists, as the latter would not be effective in shifting TNF signaling toward TNFR2 in the CNS. The gene discussed is TNFRSF1B; the disease is myeloid sarcoma.