Person: Leyva-Castillo, Juan
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
First Name
Name
Search Results
Publication IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization
(The Rockefeller University Press, 2016) Yoon, Juhan; Leyva-Castillo, Juan; Wang, Guoxing; Galand, Claire; Oyoshi, Michiko; Kumar, Lalit; Hoff, Sabine; He, Rui; Chervonsky, Alexander; Oppenheim, Joost J.; Kuchroo, Vijay; van den Brink, Marcel R.M.; Malefyt, Rene De Waal; Tessier, Philippe A.; Fuhlbrigge, Robert; Rosenstiel, Philip; Terhorst, Cox; Murphy, George; Geha, RaifAtopic 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.