How Eczema Works: Immune System, Barrier Function, and Inflammation

Eczema, also known as atopic dermatitis (AD), is a chronic or chronically relapsing inflammatory skin condition. It’s marked by intense itching, dry skin, and irritated, inflamed patches. To understand what’s happening under the skin, we need to look closely at how the immune system, skin barrier, and inflammation all interact.

If you’re just starting to explore what eczema is, you might want to check out [What Is Eczema? And What It Isn’t] and [Our Guide to the Different Types of Dermatitis] for foundational background.

What Is Eczema? A Quick Overview

At its core, eczema is a condition where the skin becomes inflamed, itchy, and sensitive to triggers. These triggers can include environmental irritants, allergens, microbes, and even stress. The key components driving eczema are a weakened skin barrier and an overactive immune response.

The Role of the Skin Barrier in Eczema

Your skin acts as the body’s first line of defense — like a sturdy brick wall that locks in moisture and keeps harmful agents out. The outermost layer, the epidermis, plays a crucial role in this protective function.

In eczema, that wall is weakened. Think of it less like a solid brick wall and more like a wicker basket — one that leaks moisture and lets in irritants, allergens, and microbes.

Why the Skin Barrier Fails

Several factors contribute to this barrier dysfunction:

• Genetics: Mutations in the filaggrin (FLG) gene, which is essential for maintaining the skin’s moisture barrier, are strongly associated with eczema. Without enough filaggrin, the skin loses hydration and becomes vulnerable to flare-ups.
• Environmental stressors: Harsh soaps, dry climates, and allergens can further weaken the skin. In eczema, the skin exhibits increased water loss, a shift in pH, reduced natural moisturizing factors, and higher permeability — all of which promote inflammation.

When the skin barrier breaks down, it creates an open invitation for irritants to penetrate deeper, setting off an immune response.

For more on how genetics shape eczema risk, see [The Role of Genetics in Eczema (And Why It Runs in Families)].

How the Immune System Plays a Role in Eczema

Eczema involves immune system dysregulation. Instead of reacting calmly to everyday stimuli, the immune system overreacts, treating harmless triggers like allergens or pollutants as threats.

Key Players in the Immune Response

• T-cells release cytokines and histamines, creating the itching, redness, and swelling that define eczema.
• Other immune cells like eosinophils, mast cells, macrophages, and dendritic cells flood the area, amplifying inflammation.
• Keratinocytes, skin cells themselves, release inflammatory molecules when under stress, joining in on the immune response.

This heightened immune activity becomes chronic, driving a continuous cycle of flare-ups and inflammation.

Th2 Dominance and Allergic Reactions

A major immune system hallmark in eczema is Th2 cell dominance. Th2 cells are designed to handle allergens, but in eczema, they go into overdrive.

• Th2 cells, along with mast cells, basophils, and ILC2s, produce inflammatory cytokines like IL-4, IL-5, IL-13, and IL-31.
• These cytokines cause itch, reduce filaggrin, and damage the skin barrier, fueling the disease.
• IL-31, in particular, is known to drive intense itching.

Additionally, alarmins like TSLP, IL-25, and IL-33, released by stressed skin cells, amplify the allergic response by activating more Th2 cells.

For a breakdown of these immune differences, see [Contact Dermatitis Mechanism vs. Atopic Dermatitis: What’s Going On Under the Skin?].

The Cycle of Inflammation in Eczema

Inflammation is the body’s way of fighting back, but in eczema, the response becomes a self-perpetuating cycle:

• Flare-ups lead to skin inflammation.
• Inflammation damages the barrier even more.
• A compromised barrier lets in more irritants, which restarts the immune reaction.

This loop — often called the itch-scratch cycle — makes eczema difficult to control without intervention.

Triggers That Aggravate Inflammation

Many triggers can worsen inflammation in eczema-prone skin, including:

• Environmental irritants (soaps, detergents, dry air)
• Allergens
• Microbes like Staphylococcus aureus
• Stress and emotional strain
• Climate changes

For a deep dive into specific flare-up causes, visit [Atopic Dermatitis: Top 10 Triggers] and [Understanding Trigger Categories: Irritants, Allergens, and More].

The Importance of Moisturizing for Barrier Function

One of the most effective steps in eczema care is regular, deep moisturizing.

• Emollient-rich creams help seal the skin and prevent moisture loss.
• Applying moisturizer after bathing helps lock in hydration.
• By reinforcing the skin barrier, moisturizers reduce inflammation and prevent new irritants from entering.

How Eczema Treatment Targets the Immune System

Modern treatments aim to calm the overactive immune system:

• Topical corticosteroids and calcineurin inhibitors help suppress local inflammation.
• Systemic therapies, including biologics and JAK inhibitors, target specific immune pathways in more severe cases.

For more information on treatment approaches, explore [Most Common Medications Prescribed for Dermatitis].

Takeaway: Understanding the Science Behind Eczema Helps You Manage It Better

Eczema is fueled by a compromised skin barrier and an overreactive immune system. Knowing how these elements work together can help you manage the condition more effectively.

By addressing both barrier repair and immune modulation, many people find significant relief. And by learning the underlying science, you can feel more in control — not just of symptoms, but of your long-term skin health.