Astrocytes are cells supporting the health and function of neurons in the brain. Upon disease or injury, they take on reactive, inflammatory states. We lack a systematic understanding of the mechanisms driving these states, and of their functional consequences.
A project led by Kun Leng and Brendan Rooney in the Kampmann lab uncovered that the endolysosomal system in inflammatory reactive astrocytes is dramatically remodeled as a consequence of mTOR signaling. This remodeling results in release of the cytokine IL-32 in association with extracellular vesicles. Intriguingly, IL-32 is a cytokine not found in mice, but only in humans and close relatives. It had previously not been studied in astrocytes, we validated that astrocytes produce IL-32 in the context of the human brain in different diseases. Future work will investigate how IL-32 affects disease processes in the brain.
The article describing these results appeared this month in the Journal of Neuroinflammation:
Leng, K., Rooney, B., McCarthy, F., Xia, W., Rose, I. V. L., Bax, S., Chin, M., Fathi, S., Herrington, K. A., Leonetti, M., Kao, A., Fancy, S. P. J., Elias, J. E., & Kampmann, M. (2024).
mTOR activation induces endolysosomal remodeling and nonclassical secretion of IL-32 via exosomes in inflammatory reactive astrocytes.
Journal of Neuroinflammation, 21(1), 198.