IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization.

Autor:	Yoon J; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Leyva-Castillo JM; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Wang G; Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Galand C; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Oyoshi MK; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Kumar L; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Hoff S; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115., He R; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Chervonsky A; Department of Pathology, University of Chicago, Chicago, IL 60637., Oppenheim JJ; Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702., Kuchroo VK; Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., van den Brink MR; Department of Immunology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065., Malefyt Rde W; Merck Research Laboratories, Palo Alto, CA 94304., Tessier PA; Centre de Recherche du Centre Hospitalier de l'Université Laval, Sainte-Foy, Quebec QC G1V 4G2, Canada., Fuhlbrigge R; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115., Rosenstiel P; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany., Terhorst C; Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Murphy G; Department of Dermatology, Harvard Medical School, Boston, MA 02115 Division of Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115., Geha RS; Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115 raif.geha@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2016 Sep 19; Vol. 213 (10), pp. 2147-66. Date of Electronic Publication: 2016 Aug 22.
DOI:	10.1084/jem.20150376
Abstrakt:	Atopic 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. (© 2016 Yoon et al.)
Databáze:	MEDLINE
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