The way in which nickel induces allergy in humans is reported this week online in Nature Immunology. Allergic responses to nickel-containing jewellery ― most commonly rings and earrings ― and cellular telephones affect millions of people worldwide.
Exposure to nickel causes burning, itching, redness, swelling and even blisters in areas of contact. Matthias Goebeler and colleagues show that nickel binds TLR4, a critical receptor normally involved in detecting pathogens. Similar to when TLR4 recognizes infectious agents, nickel also triggers an inflammatory response, which causes the symptoms associated with allergy.
The authors map binding of nickel to two specific sites on TLR4. Importantly, mutating these sites abolishes the ability of TLR4 to recognize nickel while preserving its ability to respond to pathogens. As such, site-specific TLR4 inhibition may serve as a potential strategy for therapeutic intervention without affecting vital immune responses.