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Overview

Atopic dermatitis is the most common type of eczema. It occurs when a person’s immune system causes inflammation of the skin, which also makes the skin more vulnerable to environmental irritants and allergens. Patients with atopic dermatitis often experience red, itchy skin, red and brown blotches on the skin, and raw, swollen patches on the skin. The condition can be very painful and can lead to complications like skin infections. 

Atopic dermatitis affects 15 to 20 percent of children and 1 to 3 percent of adults. Although there is no cure for atopic dermatitis, the symptoms can be treated with topical medications, phototherapy, immunosuppressant drugs, biologic drugs and steroids.

The exact cause of atopic dermatitis is unknown. The condition can run in families, which suggests there is a genetic component. In some people, a mutation in the gene that encodes the Filaggrin protein contributes to the disease.

Our Approach

Treating atopic dermatitis/eczema depends on a better understanding of the roots of the disease. LJI Professor Michael Croft, Ph.D., is investigating how proteins related to tumor necrosis factor (TNF) and others called costimulatory molecules can contribute to atopic dermatitis. Costimulatory molecules act on individual T cells, and research indicates they play a role in causing T cells to attack tissues, and T cells can make TNF-related proteins that act on tissue cells to cause inflammation.

Dr. Croft discovered many activities of OX40, a costimulatory molecule that promotes division and cytokine production in T cells. This research has led to ongoing phase II clinical trials for atopic dermatitis with a neutralizing and depleting antibody to OX40 that blocks T cell activity. 

LJI Professor Toshiaki Kawakami, M.D., PhD., has developed animal models of atopic dermatitis to study how immune cell signaling can make flare ups better or worse. His follow-up studies of human skin tissues, have confirmed that these mouse models mimic the allergic immune response seen in humans. One of Dr. Kawakami’s critical discoveries was that a protein that controls gene expression, called STAT5, drives up the number of immune cells called mast cells in the skin of some atopic dermatitis sufferers. His lab has also reported that a different signaling factor called phospholipase C-beta3 (PLC-β3) blocks STAT5. These discoveries suggest that atopic dermatitis severity could be modulated either by muffling STAT5 or boosting PLC-β3 activity. Dr. Kawakami went on to establish mouse models for eczema vaccinatum and eczema herpeticum, serious skin infections that are caused by vaccinia and herpes simplex viruses, respectively, in patients with eczema.

In collaborations with Dr. Kawakami, Dr. Croft’s lab also published research showing that LIGHT, another member of TNF family of proteins, directly controls the hyperproliferation of skin cells called keratinocytes as well as the expression of inflammatory proteins made by keratinocytes that contribute to the clinical features of atopic dermatitis. The researchers found that a therapeutic antibody that neutralizes LIGHT activity successfully suppresses disease symptoms, suggesting that therapies based on blocking LIGHT may additionally help patients suffering from atopic dermatitis.

Dr. Croft has also reported that another protein called TWEAK, which is again related to TNF, plays a role in the process to recruit immune cells into the skin. This work suggests TWEAK could be a further potential therapeutic target for the treatment of inflammatory skin diseases such as atopic dermatitis and even psoriasis.

Links:

National Eczema Association

Research Projects

Kawakami
Mouse Model of Atopic Dermatitis (AD)

As our knowledge of the FceRI-mediated signal transduction has grown for the last two decades, the need to study in

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Croft
T Cells

T cells are central to almost all immune responses. The CD4 subset is capable of directing B cell responses and

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Cheroutre
T Cells

One large subgroup of these specialized T cells is encompassed by the IEL which are located in the epithelium of

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More research projects

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TWEAKing Inflammation

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May 24, 2017 Research News
TWEAKing inflammation

LA JOLLA, CA—Superficially, psoriasis and atopic dermatitis may appear similar but their commonalities are only skin deep. Atopic dermatitis, also

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Labs

Jul 8, 2020
Kawakami Lab

Toshiaki Kawakami, M.D., Ph.D., and his team study allergic diseases such as asthma, allergic rhinitis, food allergy, and atopic dermatitis.

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Toshiaki Kawakami, M.D., Ph.D.
Professor
Center for Autoimmunity and Inflammation
Jul 8, 2020
Croft Lab

Michael Croft, Ph.D., and his team focus on a number of molecules that are members of the tumor necrosis factor (TNF) and tumor necrosis factor receptor (TNFR) family.

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Michael Croft, Ph.D.
Director, Scientific Affairs
Professor, Center for Autoimmunity and Inflammation