Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1

Item Type:	Article
Title:	Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1
Creators Name:	Haage, V. and Elmadany, N. and Roll, L. and Faissner, A. and Gutmann, D.H. and Semtner, M. and Kettenmann, H.
Abstract:	Tenascin C (Tnc) is an extracellular matrix glycoprotein, expressed in the CNS during development, as well as in the setting of inflammation, fibrosis and cancer, which operates as an activator of Toll-like receptor 4 (TLR4). Although TLR4 is highly expressed in microglia, the effect of Tnc on microglia has not been elucidated to date. Herein, we demonstrate that Tnc regulates microglial phagocytic activity at an early postnatal age (P4), and that this process is partially dependent on microglial TLR4 expression. We further show that Tnc regulates proinflammatory cytokine/chemokine production, chemotaxis and phagocytosis in primary microglia in a TLR4-dependent fashion. Moreover, Tnc induces histone-deacetylase 1 (HDAC1) expression in microglia, such that HDAC1 inhibition by MS-275 decreases Tnc-induced microglial IL-6 and TNF-α production. Finally, Tnc(-/-) cortical microglia have reduced HDAC1 expression levels at P4. Taken together, these findings establish Tnc as a regulator of microglia function during early postnatal development.
Keywords:	ECM Protein Tenascin C, Microglia, TLR4, HDAC1, Phagocytosis, Early Postnatal Development, Animals, Mice
Source:	Brain Behavior and Immunity
ISSN:	0889-1591
Publisher:	Elsevier / Academic Press
Volume:	81
Page Range:	470-483
Date:	October 2019
Official Publication:	https://doi.org/10.1016/j.bbi.2019.06.047
PubMed:	View item in PubMed

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