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, keratinocytesinitiate 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 keratinocytefunction has yet to be elucidated. To investigate how IL-6Rα function in keratinocytesinfluences 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 keratinocyteIL-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 keratinocytederived IL-6Rα.