No abstract

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that has increased in prevalence over the last half century. A growing body of evidence suggests that there are a variety of defects in the innate immune system that collectively affect the development and severity of AD. The reduction in antimicrobial peptides, diminished recruitment of innate immune cells (PMNs, pDC, and NK cells) to the skin, epithelial barrier disruption, and TLR2 defects are just some of the credible explanations for AD patients' susceptibility to pathogens such as Staphylococcus aureus, herpes simplex virus, and vaccinia virus. Although the focus for several years has been to identify defects in the innate immune system that might explain AD patients' susceptibility to cutaneous pathogens, it has become clear that some innate immune defects might promote inflammation and thereby aggravate or even induce the development of AD. Here we review the innate immune system, and highlight many of the potential innate networks that may be important in AD patients susceptible to cutaneous pathogens.

Respiratory epithelial cells (EpCs) orchestrate airway mucosal inflammation in response to diverse environmental stimuli, but how distinct EpC programs are regulated remains poorly understood. Here, we report that inhalation of aeroallergens leads to expansion of airway brush cells (BrCs), specialized chemosensory EpCs and the dominant epithelial source of interleukin-25 (IL-25). BrC expansion was attenuated in mice lacking either LTC4 synthase, the biosynthetic enzyme required for cysteinyl leukotriene (CysLT) generation, or the EpC receptor for leukotriene E4 (LTE4), CysLT3R. LTE4 inhalation was sufficient to elicit CysLT3R-dependent BrC expansion in the murine airway through an IL-25–dependent but STAT6-independent signaling pathway. Last, blockade of IL-25 attenuated both aeroallergen and LTE4-elicited CysLT3R-dependent type 2 lung inflammation. These results demonstrate that CysLT3R senses the endogenously generated lipid ligand LTE4 and regulates airway BrC number and function.