Yoon, JuhanLeyva-Castillo, JuanWang, GuoxingGaland, ClaireOyoshi, MichikoKumar, LalitHoff, SabineHe, RuiChervonsky, AlexanderOppenheim, Joost J.Kuchroo, Vijayvan den Brink, Marcel R.M.Malefyt, Rene De WaalTessier, Philippe A.Fuhlbrigge, RobertRosenstiel, PhilipTerhorst, CoxMurphy, GeorgeGeha, Raif2017-04-062016Yoon, J., J. M. Leyva-Castillo, G. Wang, C. Galand, M. K. Oyoshi, L. Kumar, S. Hoff, et al. 2016. “IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization.” The Journal of Experimental Medicine 213 (10): 2147-2166. doi:10.1084/jem.20150376. http://dx.doi.org/10.1084/jem.20150376.http://nrs.harvard.edu/urn-3:HUL.InstRepos:32072124Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, a cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD skin lesions. We show that application of antigen to mouse skin subjected to tape stripping, a surrogate for scratching, induces an IL-22 response that drives epidermal hyperplasia and keratinocyte proliferation in a mouse model of skin inflammation that shares many features of AD. DC-derived IL-23 is known to act on CD4+ T cells to induce IL-22 production. However, the mechanisms that drive IL-23 production by skin DCs in response to cutaneous sensitization are not well understood. We demonstrate that IL-23 released by keratinocytes in response to endogenous TLR4 ligands causes skin DCs, which selectively express IL-23R, to up-regulate their endogenous IL-23 production and drive an IL-22 response in naive CD4+ T cells that mediates epidermal thickening. We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD.en-USArticleJournal Article2017-04-0610.1084/jem.20150376