How Your Body’s Own Recycling System Could Calm Inflammation Without Weakening Immunity

Most anti-inflammatory drugs work the same way: they turn down the immune system as a whole, which calms the flare-up but also leaves patients more vulnerable to infection. Researchers at VIB and KU Leuven, working with international collaborators, have found a way around that trade-off. By targeting a specific type of blood vessel rather than immune cells themselves, they were able to reduce inflammation in mice with psoriasis while leaving the rest of the immune system untouched. The findings, published in Immunity, point to a promising new route for treating chronic inflammatory and autoimmune disease.

The vessels that decide who gets into the lymph nodes

Lymph nodes are the immune system’s checkpoints, filtering lymph and blood for pathogens and coordinating the response against them. Immune cells reach the lymph nodes through specialized blood vessels called high endothelial venules, or HEVs. These vessels are studded with adhesion molecules known as peripheral node addressins (PNAd), which act like a sticky coating that pulls circulating lymphocytes out of the bloodstream and into the node.

First author Dr Kathryn Jacobs (VIB-KU Leuven) describes PNAd as the signal that tells immune cells to leave the bloodstream and enter the lymph node.

Cellular recycling keeps the gates open

During infection, HEVs ramp up PNAd production to pull in more lymphocytes and strengthen the immune response, but in chronic inflammatory and autoimmune disease, that same mechanism keeps immune cells flooding in long after they’re needed, worsening symptoms. What controls PNAd production had remained largely a mystery.

The team, led by Prof Gabriele Bergers at the VIB-KU Leuven Center for Cancer Biology, traced it back to autophagy: the cell’s internal recycling process for clearing out old or damaged components. When the researchers blocked autophagy specifically in HEVs, PNAd production dropped, the vessels lost their specialized identity, and far fewer lymphocytes were able to enter the lymph nodes. Notably, blocking autophagy in other blood vessel types has the opposite effect, ramping inflammation up rather than down — a sign that HEVs handle autophagy in a distinct way.

Testing the idea in psoriasis

To see whether disrupting HEVs could treat disease without touching the immune system directly, the team turned to psoriasis, a chronic autoimmune skin condition affecting an estimated 125 million people worldwide. HEVs can form within psoriatic skin lesions, where they recruit immune cells and keep local inflammation going. Existing treatments mostly work by suppressing immunity broadly, which raises the risk of serious infection.

In a mouse model of psoriasis, blocking autophagy in HEVs cut immune cell recruitment and reduced skin inflammation. The researchers then tested a pharmacological approach: a drug that blocks a signaling receptor HEVs need to form and function. It reproduced the same effect, lowering both immune cell infiltration and inflammation.

Prof Gabriele Bergers says the results point to HEVs as a promising therapeutic target, though more work is needed before the approach could reach patients.

What’s next

The team hopes to refine the LTβR-blocking drugs used in the study. A better antagonist, Dr Jacobs suggests, could potentially help with a range of autoimmune diseases beyond psoriasis — dialing down the immune response without disarming the immune cells that patients still need for everyday protection.

Original paper: Autophagy maintains high endothelial venule identity and function during inflammation, published in Immunity (DOI: 10.1016/j.immuni.2026.06.020). 

Source: How Your Body’s Own Recycling System Could Calm Inflammation Without Weakening Immunity