Human Beta-Defensin
2

Before 1997

The Puzzle of Psoriasis

A Question Hidden in Plain Sight

Psoriasis affects over 100 million people worldwide. Their skin turns red, swollen, and covered in silvery scales. The outer layer of skin grows too fast, piling up in thick patches that crack and bleed.

By all logic, these patients should be constantly fighting skin infections. Their skin barrier is broken. Bacteria should pour in through every crack. Yet dermatologists had noticed something strange for decades: psoriasis patients almost never get bacterial skin infections.

Meanwhile, patients with eczema — another common skin disease — suffered the opposite problem. Their skin was constantly infected with staph bacteria, even though their skin looked less damaged than psoriasis patients. Nobody could explain why.

At the University of Kiel in northern Germany, Professor Enno Christophers kept asking his colleagues the same question: What is protecting psoriatic skin? Most shrugged it off. But a young researcher named Jürgen Harder decided to find out.

The Breakthrough

Mining for Gold in Skin Scales

A Discovery Published in Nature

Harder's approach was unconventional. He collected the dry, flaky scales that psoriasis patients shed from their skin — material that most people would throw away. He ground up these scales, dissolved them, and ran the mixture through a series of filters designed to catch any molecule that could kill bacteria.

What he found made history. Hidden in those discarded skin flakes was a tiny protein — just 41 amino acids long — that killed bacteria on contact. When he tested it against common skin pathogens like E. coli and the yeast Candida, it wiped them out.

Harder and his mentor Schröder recognized the protein as a new member of the defensin family — nature's oldest group of antimicrobial peptides, found in everything from plants to insects to humans. They named it Human Beta-Defensin 2, or HBD-2.

The paper was published in Nature in 1997 with a simple but groundbreaking title: 'A peptide antibiotic from human skin.' It was the first time anyone had proven that human skin cells manufacture their own antibiotics.

The Trials

The Alarm System

A Weapon That Only Fires When Needed

What made HBD-2 truly remarkable was that healthy skin barely made it. Unlike HBD-1, which is always present at low levels, HBD-2 was an 'inducible' defensin — it only switched on when skin detected danger.

When bacteria touched skin cells, or when the immune system released alarm signals like TNF-alpha and interleukin-1, skin cells ramped up HBD-2 production dramatically. It was like an air raid siren that activated anti-aircraft guns.

Then came the breakthrough that connected everything. In 2002, Peck Ong published a landmark study in the New England Journal of Medicine. He compared defensin levels in psoriasis patients versus eczema patients. The results were stunning.

Psoriasis skin was flooded with HBD-2 and LL-37. Eczema skin made almost none. This finally explained the mystery: psoriasis patients were protected because their inflamed skin was pumping out natural antibiotics. Eczema patients were vulnerable because their alarm system was broken.

The Crisis

The Double-Edged Sword

When Protection Becomes the Problem

As research deepened, scientists discovered a troubling side to the defensin story. In psoriasis, the immune system was making too much HBD-2 — and the peptide wasn't just killing bacteria. It was also calling in more immune cells, which caused more inflammation, which triggered even more HBD-2 production.

This created a vicious cycle. The very weapon that protected psoriasis patients from infections was also fueling the disease itself. Studies found that people with extra copies of the defensin gene were more likely to develop psoriasis in the first place.

Researchers also discovered that HBD-2 could attract immature immune cells called dendritic cells and memory T cells by hooking onto a sensor called CCR6. This meant HBD-2 wasn't just an antibiotic — it was a bridge between the body's fast-acting first defenses and its slower, more targeted immune response.

The challenge became clear: How do you harness HBD-2's bacteria-killing power without triggering unwanted inflammation?

The Legacy

Unlocking the Code

From Understanding to Application

Today, HBD-2 research has branched into several exciting directions. Scientists are exploring whether boosting defensin production could help eczema patients fight off the staph infections that make their disease worse. Others are investigating synthetic versions of HBD-2 as alternatives to failing antibiotics.

One of the most promising discoveries is that HBD-2 doesn't just kill bacteria directly — it also protects the skin barrier from damage caused by bacterial toxins. Studies have shown that it blocks a bacterial weapon called V8 protease, which staph bacteria use to chew through skin proteins.

Researchers are also using HBD-2 levels as a biomarker — a measurable signal — to track how severe psoriasis is and whether treatments are working. Blood tests for HBD-2 could give doctors a simple way to monitor skin diseases without taking biopsies.

What started with a curious question about psoriasis has grown into one of the most important stories in skin science — proving that our largest organ is also one of our most active defenders.