Keratinocyte-specific deletion of the IL-6RΑ exacerbates the inflammatory response during irritant contact dermatitis

Abstract

Irritant Contact Dermatitis (ICD) is the most common occupational skin disorder. During ICD, keratinocytes initiate the inflammatory cascade by producing cytokines including IL-6. This laboratory previously reported that IL-6 deficiency exacerbates skin inflammation during ICD, yet the role of the IL-6Rα in keratinocyte function has yet to be elucidated. To investigate how IL-6Rα function in keratinocytes influences the inflammatory response during ICD, keratinocyte-specific IL-6Rα KO (IL6ra^Δker) and WT mice were exposed to two well-known occupational irritants; JP-8 jet fuel, and benzalkonium chloride (BKC), or acetone control for three days. Dermatitis lesions were collected and flow cytometric and immunohistochemical analyses revealed that IL6ra^Δker skin displayed increased populations of CD11b⁺CD45⁺ and F4/80⁺ cells respectively relative to WT. However, IL6ra^Δker mouse skin contained reduced numbers of γδ T cells relative to WT. Furthermore, IL6ra^Δker skin expressed increased levels of pro-inflammatory cytokines including IL-1β, IL-22, and CCL4 but decreased levels of anti-inflammatory cytokines IL-4 and IL-10. These results indicate that epidermal keratinocyte IL-6Rα function modulates epidermal hyperplasia, immune cell infiltration into skin and cytokine expression during ICD and suggests that the previously reported protective effect of IL-6 during ICD might be mediated primarily by keratinocyte derived IL-6Rα.

Keywords: Inflammation; Irritant contact dermatitis; Keratinocytes; Skin.