IL-36α is involved in hapten-specific T-cell induction, but not local inflammation, during contact hypersensitivity

Levels of IL36 alpha are known to be increased in specimens from patients with atopic dermatitis and psoriasis. In addition, it has been reported that IL-36 alpha is crucial for development of imiquimod-induced psoriatic dermatitis in mice. On the other hand, the role of IL-36 alpha in induction of allergic contact dermatitis/contact hypersensitivity (ACD/CHS) is poorly understood. We found that IL-36 alpha was produced in keratinocytes of mice during imiquimod-induced psoriatic dermatitis, but it was hardly detectable in the skin of mice during either fluorescein isothiocyanate (FITC)- or 1-fluoro-2, 4-dinitrobenzene (DNFB)-induced CHS. Although IL-36 alpha can enhance activation of dendritic cells (DCs) and T cells, in CHS, IL-36a was not essential for DC migration from the skin to draining LNs, but it was required for induction or activation of hapten-specific T cells such as Th/Tcl or Th17 cells. However, local inflammation, assessed by measurement of ear skin thickness, was comparable between wild-type and IL-36 alpha-deficient mice during both FITC- and DNFB-induced CHS. These observations indicate that IL-36 alpha is involved in induction and/or activation of hapten-specific T-cell subsets in the sensitization phase of CHS, but not essential for induction of local inflammation in the elicitation phase. (C) 2018 Elsevier Inc. All rights reserved.