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Autophagy maintains HEV identity and function during inflammation.

ABSTRACT: High endothelial venules (HEVs) play a crucial role in immunological responses by facilitating lymphocyte entry into the lymph node through display of peripheral node addressins (PNAd). During inflammation, the HEV network expands and upregulates additional adhesion molecules for proper T cell influx, but the underlying mechanisms remain poorly understood. Here we report that autophagy is essential for the proper expansion and functioning of HEVs using single-cell transcriptomics, intravital imaging, and novel inducible HEV tracer mouse models. We demonstrate that lack of autophagy leads to a loss of HEV phenotype and functionality through reduced lymphotoxin beta receptor and Unfolded Protein Response activation, which contribute to decreased production of PNAd. This autophagy-dependent mechanism maintains HEV identity during inflammatory stress. These findings reveal that blocking HEV expansion can be exploited therapeutically, as demonstrated in a psoriasis model where it resulted in less severe disease phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE300153 | GEO | 2026/08/10

REPOSITORIES: GEO

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