SorLA restricts TNFα release from microglia to shape a glioma-supportive brain microenvironment.

Autor:	Kaminska P; Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland.; Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland., Ovesen PL; Max-Delbrueck Center for Molecular Medicine, 13125, Berlin, Germany., Jakiel M; Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland.; Institute of Computer Science, 01-248, Warsaw, Poland., Obrebski T; Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland., Schmidt V; Max-Delbrueck Center for Molecular Medicine, 13125, Berlin, Germany., Draminski M; Institute of Computer Science, 01-248, Warsaw, Poland., Bilska AG; Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland.; Museum and Institute of Zoology, Polish Academy of Sciences, 00-679, Warsaw, Poland., Bieniek M; Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland., Anink J; Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, 1105AZ, Amsterdam, The Netherlands., Paterczyk B; Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland., Jensen AMG; Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark., Piatek S; Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland., Andersen OM; Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark., Aronica E; Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, 1105AZ, Amsterdam, The Netherlands.; Stichting Epilepsie Instellingen Nederland, 2103 SW, Heemstede, The Netherlands., Willnow TE; Max-Delbrueck Center for Molecular Medicine, 13125, Berlin, Germany.; Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark., Kaminska B; Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland., Dabrowski MJ; Institute of Computer Science, 01-248, Warsaw, Poland., Malik AR; Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland. ar.malik@uw.edu.pl.; Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland. ar.malik@uw.edu.pl.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 May; Vol. 25 (5), pp. 2278-2305. Date of Electronic Publication: 2024 Mar 18.
DOI:	10.1038/s44319-024-00117-6
Abstrakt:	SorLA, encoded by the gene SORL1, is an intracellular sorting receptor of the VPS10P domain receptor gene family. Although SorLA is best recognized for its ability to shuttle target proteins between intracellular compartments in neurons, recent data suggest that also its microglial expression can be of high relevance for the pathogenesis of brain diseases, including glioblastoma (GBM). Here, we interrogated the impact of SorLA on the functional properties of glioma-associated microglia and macrophages (GAMs). In the GBM microenvironment, GAMs are re-programmed and lose the ability to elicit anti-tumor responses. Instead, they acquire a glioma-supporting phenotype, which is a key mechanism promoting glioma progression. Our re-analysis of published scRNA-seq data from GBM patients revealed that functional phenotypes of GAMs are linked to the level of SORL1 expression, which was further confirmed using in vitro models. Moreover, we demonstrate that SorLA restrains secretion of TNFα from microglia to restrict the inflammatory potential of these cells. Finally, we show that loss of SorLA exacerbates the pro-inflammatory response of microglia in the murine model of glioma and suppresses tumor growth. (© 2024. The Author(s).)
Databáze:	MEDLINE
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