ASTROCYTE-TARGETED PRODUCTION OF IL-10 INDUCES CHANGES IN MICROGLIAL REACTIVITY AND REDUCES MOTOR NEURON DEATH AFTER FACIAL NERVE AXOTOMY (#345)
Interleukin-10 (IL-10) is a cytokine that plays a crucial role in regulating the inflammatory response and immune reactions. In the central nervous system (CNS), IL-10 is mainly produced by astrocytes and microglia and its upregulation has been demonstrated after various insults, such as experimental autoimmune encephalomyelitis, middle cerebral artery occlusion, excitotoxicity and traumatic brain injury. To better understand the effects of IL-10 in the normal and injured CNS, we generated transgenic mice expressing the murine IL10 gene under the transcriptional control of the GFAP promoter (GFAP-IL10Tg). Previous studies by our group demonstrated specific changes in microglial phenotype under basal conditions in GFAP-IL10Tg mice. The objective of the present study was to investigate the effects of local astrocyte-targeted IL-10 production on microglial activation, neuronal degeneration and leukocyte recruitment after experimental axotomy. Our results showed that after facial nerve axotomy, GFAP-IL10Tg mice showed remarkable changes in the expression of different molecules associated with the microglial activation pattern, such as CD16/32, CD18 and MHC-II, as well as in the number of microglial clusters and in microglial cell density. Furthermore, a higher CD3+ lymphocyte infiltration was observed on the axotomized FN of GFAP-IL10Tg mice. These changes in microglial activation and lymphocyte recruitment correlated with a reduced motor neuron death at 21 dpi. Altogether, our findings suggest that astrocyte-targeted production of IL-10 impacted the microglial response and lymphocyte recruitment and culminated in a beneficial effect on neuronal survival.