IL-22 derived from γδ T cells restrictsStaphylococcus aureusinfection of mechanically injured skin

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Abstract

Background:

Staphylococcus aureusis an opportunistic pathogen that colonizes the skin of patients with atopic dermatitis (AD) and aggravates their disease. Neutrophils and the cytokines IL-17A and IL-17F, which drive the expression of the neutrophil-attracting chemokines, are important for the clearance ofS aureusinfection. The cytokine IL-22 is often coproduced by IL-17–secreting cells. The levels of IL-22 are elevated in AD skin lesions.

Objective:

We sought to determine the role of IL-22 in the clearance ofS aureusinfection of mouse skin subjected to tape stripping, a surrogate for scratching, a cardinal feature of AD.

Methods:

S aureuswas applied to the tape-stripped skin of wild-type andIl22−/−mice. Bacterial burden was evaluated by enumerating colony-forming units. Quantitative PCR and ELISA were performed to quantifyIl22mRNA and IL-22 protein in mouse and human skin. Flow cytometry was used to enumerate neutrophils in the skin.

Results:

Scratching the skin of healthy adults and tape stripping of mouse skin induced local expression ofIl22mRNA and IL-22 protein. Induction ofIl22expression by tape stripping was dependent on IL-23 and γδ T cells. Clearance ofS aureusfrom tape-stripped skin was significantly impaired inIl22−/−mice. Neutrophil infiltration and upregulation of expression of genes encoding the antimicrobial peptides antigen-6/urokinase-type plasminogen activator receptor related protein-1 and β-DEFENSIN 14 and the chemokine (C-X-C motif) ligand following tape stripping were significantly impaired inIl22−/−mice.

Conclusions:

These findings show that IL-22 is important for limiting the growth ofS aureuson mechanically injured skin and caution that IL-23 and IL-22 blockade in patients with AD may enhance susceptibility to staphylococcal skin infection.

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