How the body’s natural recycling system may reduce inflammation

Leuven, Belgium — 28 July 2026 — Researchers from VIB and KU Leuven, working with international collaborators, report that disabling autophagy in a specific class of blood vessels can dampen inflammation in a mouse model of psoriasis. Published in Immunity, the study highlights an immune-regulating strategy that reduces inflammatory recruitment without broadly suppressing immune function.

The work centers on lymph nodes, where immune responses are organized and pathogens and abnormal cells are filtered from lymphatic and blood-borne material. A key entry route for circulating lymphocytes into lymph nodes is through specialized post-capillary venules known as high endothelial venules (HEVs).

HEVs express peripheral node addressins (PNAd) on their surface, which act as adhesion cues that help lymphocytes exit the bloodstream and home to lymph nodes. As inflammation develops, HEVs can increase PNAd expression to recruit more lymphocytes—an effect that is beneficial for acute defense but can become harmful in chronic inflammatory or autoimmune settings.

The researchers found that autophagy is required to sustain HEV identity and function during inflammatory stress. When autophagy was blocked, PNAd levels declined, HEVs lost their specialized phenotype, and far fewer lymphocytes were able to enter lymph nodes.

Crucially, the team reports that the consequences of autophagy inhibition depend on vessel type: blocking autophagy in other vascular contexts can enhance inflammatory signaling, whereas HEVs uniquely rely on autophagy to maintain their immune-recruiting program. This specificity points to a therapeutic window for targeting inflammation without globally disabling immune surveillance.

To test clinical relevance, the authors manipulated HEV autophagy in mice with psoriasis-like disease. The approach reduced immune-cell infiltration into psoriatic skin lesions and lowered local inflammatory pathology.

For translational direction, the team also used a pharmacological intervention aimed at an HEV-dependent signaling receptor necessary for vessel formation and function. This treatment recapitulated the autophagy blockade phenotype, decreasing immune recruitment and improving skin inflammation in the same experimental framework.

The study suggests that HEVs, rather than immune cells directly, could be an attractive target class for future therapies aimed at chronic inflammatory and autoimmune disorders. By modulating the vascular gateways that control where immune cells go, the strategy may limit disease-driving recruitment while preserving broader immune competence.