5. Secondary lymphoid tissue chemokine (CCL21) in neuron-microglia signalling

Abstract

Microglia is considered to be the sentinel of the CNS. Accordingly, microglia activity aims to protect and to restore, and only in case of uncontrolled or impaired microglia function, these cells may have detrimental effects. The control of microglia activity is thus an important issue to understand. The family of chemokines are versatile signals specialized to control cell-cell interactions. Neurons express a variety of chemokines in a temporarily and spatially regulated manner and microglia respond to these messengers via the appropriate receptors. Here, we would like to discuss the function of CCL21 in the brain. In the peripheral immune system, CCL21 is known as homeostatic chemokine that is constitutively expressed in secondary lymphoid tissue. CCL21 is important for the development of lymphoid structures and several aspects of the specific immune response. In the brain, CCL21 is specifically expressed in endangered or damaged neurons. Our recent data indicate that neuronal CCL21 is sorted in large-dense core vesicles, transported into neuronal axons, and released in a regulated manner. Microglia in vitro and in situ responds to CCL21 stimulation with calcium signaling and chemotaxis via the chemokine receptor CXCR3. The activity of microglia in response to neuronal damage (in vitro, in situ, and in vivo) is significantly changed when CCL21-CXCR3 signaling is disturbed. Due to these data we suggest a brain-specific function of CCL21 in directed neuron-microglia communication after neuronal injury.