Blood monocytes expressing CCR6 and monocyte-derived dendritic cells in dermis and epidermis are critical for IL-23-induced psoriasis-like inflammation in mice (CAM5P.238)

Abstract

Abstract Human studies have implicated IL-23 in psoriasis, and injecting IL-23 in mouse skin produces IL-22-dependent, psoriasis-like inflammation. IL-23 injection leads to accumulation of dendritic cells (DCs), which are also abundant in psoriatic skin, and depleting CD11c+ cells blocked IL-23-induced IL-22 and inflammation. In analyzing myeloid cells, we found monocyte-derived langerin+ cells (mLCs) appearing in the epidermis and more of other monocyte-derived cells, including mDCs, plus non-monocyte derived DCs in the dermis after IL-23 injection. Batf3-/-, diphtheria toxin-treated Bdca2-DTR, and Flt3l-/- mice, which lack CD103+ cDCs, pDCs, and all cDCs and pDCs, respectively, each showed only modest protection against IL-23-induced changes. Although depleting conventional LCs alone had no effect, inflammation was much diminished in langerin-DTR mice also depleted of mLCs. Together, these data suggested that CD11c+ mDCs and mLCs contributed significantly to pathology. We have reported that Ccr6-/- mice are resistant to IL-23-induced pathology, and the skin of Ccr6-/- mice showed no changes in DCs after IL-23 injection. Using Ccr6-EGFP mice, we identified expression of Ccr6 in blood monocytes, and found that Ccr6+/+, but not Ccr6-/- monocytes restored inflammation when injected i.v. into Ccr6-/- mice. Together, our data suggest that blood monocytes are recruited to inflamed skin using CCR6 and give rise to mDCs and mLCs, which are critical for IL-23-induced psoriasis-like pathology.