Topical exposure to the quaternary ammonium compound didecyldimethylammonium chloride augments dermal type 2 innate lymphoid cell populations

Abstract

Abstract Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound used in commercial and industrial products for its antimicrobial properties. Clinical reports suggest that topical exposure to DDAC can resultin immediate and delayed type hypersensitivity, and recently our laboratory has confirmed that DDAC is a strong non-IgE mediated sensitizer in mice at relevant human exposure concentrations. Here, we further investigate the mechanism of DDAC induced hypersensitivity in mice, focusing on dermal immune responses. Gene expression analysis shows significant reduction in epithelial Cdh1, and increases in Tslp and Ccl17 following DDAC application to the skin, indicating that dermal type 2 innate lymphoid cells (ILC2s) may be involved in DDAC-induced hypersensitivity. Phenotypic analysis of dermal ILC2s shows that these cells are rapidly activated with increased expression of CD25, ICOS, and KLRG1 occurring by 24 hours post DDAC exposure. Increases in ILC2 number were observed following 2 weeks of DDAC exposure and found to persist for up to 2 weeks in the absence of DDAC and Tslp. Additionally, the phenotype of these cells suggests a potential for longevity (reduced KLRG1 and increased CD127) and enhanced activity (increased ICOS), which may influence future sensitization events. ILC2s have been previously implicated to play a role in IgE-independent allergic responses, but to our knowledge have not been investigated in chemical allergy. These results indicate that skin resident ILC2s may play a role in the development of the hypersensitivity response to DDAC and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects.