Ischemia-induced neuronal expression of the microglia attracting chemokinesecondary lymphoid-tissue chemokine (SLC)

Recently, it has been demonstrated that secondary lymphoid-tissue chemokine (SLC) is constitutively expressed in secondary lymphoid organs and control s the homing of naive T-cells and mature dendritic cells. By screening cDNA isolated from ischemic mouse brain, we found expression of SLC mRNA 6 h up to 4 days after the onset of ischemia. In situ hybridization combined with immunohistochemistry showed neurons expressing SLC mRNA in the ischemic ar ea of the cortex. SLC mRNA expression was also found in cultured neurones a fter various treatments known to induce neuronal death, but not in cultured glial cells. Stimulation with SLC induced intracellular calcium transients and chemotaxis in cultured microglia. Since mRNA encoding CXCR3, an altern ative receptor for SLC, but no CCR7 mRNA was found in microglia, we suggest that the effects of SLC on microglia are mediated by CXCR3. This assumptio n was corroborated by cross-desensitization experiments using IP-10 as a li gand for CXCR3. The inducible expression of SLC in neurones acting on micro glia suggests a new and important role of SLC in the neuroimmune system. We propose that SLC is part of a neurone-microglia signaling system which is related to pathological conditions of the brain like ischemia. GLIA 34:121- 133, 2001. (C) 2001 Wiley-Liss, Inc.