Understanding celiac disease

September 14, 2004

Two separate research studies published in the September issue of Immunity provide significant new details about why immune cells attack the body's own healthy tissues in response to a harmless substance that the immune system mistakenly perceives as a threat. The results are likely to further research efforts designed to combat and hopefully prevent autoimmune disorders like celiac disease.

Celiac disease is characterized by abnormalities of the small intestine that interfere with absorption of nutrients from food. When people with celiac disease eat foods containing gluten, a major protein in wheat, rye, and barley products, their immune system attacks and damages the lining of the small intestine. Development of this disease has been linked to the transformation of normal immune cells, called cytotoxic T lymphocytes (CTLs), that normally protect the body from ingested pathogens into renegade lymphokine-activated killer (LAK) cells that harm the intestinal lining. However, the processes contributing to active destruction of healthy tissue are not well understood.

A research study headed by Dr. Bana Jabri from the Department of Pathology at the University of Chicago examined a receptor on CTL cells called NKG2D that can be activated by stress-induced chemicals and has been linked to tissue damage. The researchers found that the immune stimulator IL15 induces a series of biochemical changes in the NKG2D signaling pathway that converts CTL cells into LAK cells in cells grown in the laboratory and in patients with celiac disease. "These findings may provide the basis for novel therapeutic approaches in celiac disease aiming at suppressing uncontrolled CTL activation and conversion into LAK by blocking IL15 or NKG2D," suggests Dr. Jabri.

A second study led by Dr. Sophie Caillat-Zucman from Equipe Avenir-Inserm in Paris, France demonstrated that MICA, a molecule that interacts with NKG2D on CTL cells, is present in elevated amounts in the cells that line the intestines of celiac patients and can be stimulated by wheat gluten, via IL15, in cells grown in the laboratory. By expressing MICA, the intestinal cells provide a target for CTL cells that are simultaneously stimulated by IL15 to attack the intestinal tissue. The authors also suggest that controlling this process may help protect the intestinal lining of celiac patients from the damaging effects of gluten.

Bertrand Meresse, Zhangguo Chen, Cezary Ciszewski, Maria Tretiakova, Govind Bhagat, Thomas N. Krausz, David H. Raulet, Lewis L. Lanier, Veronika Groh, Thomas Spies, Ellen C. Ebert, Peter H. Green, and Bana Jabri: "Coordinated Induction by IL15 of a TCR-Independent NKG2D Signaling Pathway Converts CTL into Lymphokine-Activated Killer Cells in Celiac Disease"

Sophie Hüe, Jean-Jacques Mention, Renato C. Monteiro, ShaoLing Zhang, Christophe Cellier, Jacques Schmitz, Virginie Verkarre, Nassima Fodil, Seiamak Bahram, Nadine Cerf-Bensussan, and Sophie Caillat-Zucman: "A Direct Role for nkg2d/mica InteractionIn Villous Atrophy during Celiac Disease"
-end-
Publishing in Immunity, Volume 21, Number 3, September 2004.

Cell Press

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