Leukotriene B4: A Central Recruiter of Neutrophils in Allergic Dermatitis

LTB4-mediated attraction of neutrophils to skin subjected to tape stripping, a surrogate for scratching, is essential for development of allergic inflammation.

The itch–scratch cycle is a key component of exacerbations of atopic dermatitis (AD). Influx of T cells, particularly T helper 2 (Th2) cells, with eosinophils, has long been known to play a role in AD. Oyoshi and colleagues found a surprising new player.

They found that neutrophils are recruited to the superficial dermis of scratched skin in humans and tape-stripped skin in mice. Leukotriene B4 (LTB4), a known neutrophil chemoattractant, and its receptor BLT1 were elevated in such skin. LTB4 is generated from innate immune cells such as neutrophils, in response to a variety of stimuli.

Using a classic model of allergic dermatitis in mice, the investigators epicutaneously administered an ovalbumin challenge to sensitized mice. Ovalbumin-specific T cells are easily identified, providing a basis for measuring allergen responses. When the researchers transferred CD4+ T cells to mice lacking Ltb4, the mice showed no signs of allergic dermatitis. However, cotransferring normal neutrophils to areas of challenge reversed this effect. Conversely, transferring CD4+ T cells from ovalbumin-sensitized Ltb4-deficient mice to wild-type mice also failed to elicit a response. Taken together, these findings indicate that LTB4 function, through its receptor BLT1, is required for neutrophil recruitment to areas of injury or challenge, subsequent recruitment of CD4+ T cells, and Th2 inflammation.

CITATION(S):

Oyoshi MK et al. Leukotriene B4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation. Immunity 2012 Oct 19; 37:747.