Nickel Allergy Linked to Innate Immune Response

Image: Wikimedia Commons - Nicor
Nickel allergy is one of the most common causes of allergic contact dermatitis and a team led by researchers at the University of Giessen have now shown that the response is linked to activation of a single receptor, toll-like receptor 4 (TLR4).

The family of toll-like receptors normally recognizes structurally similar molecules derived from microbial pathogens and plays a key role in host defense. The team showed that nickel directly activated human, but not mouse, TLR4 and studies with mutant proteins showed that non-conserved histidine residues at positions 456 and 458 were necessary for activation of human TLR4. Wild type mice do not show an allergy to nickel but transgenic mice expressing human, rather than mouse, TLR4 could be efficiently sensitized to the metal. This is the first time that an inorganic substance has been shown to activate this innate immune pathway and, since histidines 456 and 458 are not essential for responses to microbial lipopolysaccharide, the authors suggest that site-specific inhibition of TLR4 could provide a potential strategy for treatment of nickel allergy, which would not compromise normal immune responses. Nickel allergy affects millions of people and is often associated with earrings and jewellery for other body piercings.

The study is published in the journal Nature Immunology.

Allergy Drugs May Treat Obesity and Type 2 Diabetes

mast cellsMast cells are best known for their role in allergic responses but a new study by researchers at Brigham and Women’s Hospital and colleagues has now shown a link with diet-induced obesity and type 2 diabetes. Writing in the July edition of Nature Medicine, they show that mast cells are far more abundant in white adipose tissue from obese humans and mice than in tissue from normal weight individuals. ketotifen and cromolyn structures

In mice on a high calorie diet, treatment for two months with either of the allergy treatments, ketotifen fumarate or cromolyn, led to significant weight loss and improvement in diabetic markers compared with control animals. More dramatic improvements were seen if the animals were also switched to a reduced fat diet.

In further studies, the team showed that mice which lack mature mast cells neither became obese nor developed diabetes over a three month period, despite being fed a Western diet rich in sugars and fats. As a next step towards possible testing in humans, the researchers plan to study the effect of the compounds on obese and diabetic non-human primates.

Ketotifen fumarate and cromolyn are both used in anti-allergy eye drops, and to prevent asthma attacks. Although both stabilise mast cells, the exact mechanisms by which they achieve this are somewhat different.