title: Epidermal expression of I-TAC (Cxcl11) instructs adaptive Th2-type immunity.
abstract: To decipher early promoters of the local microenvironment for Th2-type immunity, we wanted to identify gene patterns that were induced by Leishmania major in the infected skin of susceptible, Th2-prone BALB/c, but not of resistant, Th1-prone C57BL/6 mice. We found a marked up-regulation of the chemokine I-TAC (Cxcl11) during the first 2 d of infection in the epidermis of susceptible but not of resistant mice. Accordingly, local injection of I-TAC (2×1 μg) in resistant mice on the first day of infection resulted in a Th2-driven, sustained deterioration of disease and dramatically enhanced parasite levels. On the cellular level, I-TAC decreased IL-12 production by dendritic cells (DCs) in skin-draining lymph nodes and by DCs in vitro. Thus, we demonstrate for the first time that epidermis-derived I-TAC triggers a sustained Th2-response that determines the outcome of a complex immunological process.
authors.affiliation: 2Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany. jan.ehrchen@ukmuenster.de.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Roebrock
authors.forename: Cord
authors.initials: C
authors.lastname: Sunderkötter
authors.forename: Niels-Arne
authors.initials: NA
authors.lastname: Münck
authors.forename: Marc
authors.initials: M
authors.lastname: Wolf
authors.forename: Nadine
authors.initials: N
authors.lastname: Nippe
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Barczyk
authors.forename: Georg
authors.initials: G
authors.lastname: Varga
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Jan
authors.initials: J
authors.lastname: Ehrchen
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology*; D000818:Animals; D054371:Chemokine CXCL11 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000276:immunology; D006790:Host-Parasite Interactions / Q000276:immunology; D017403:In Situ Hybridization; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology / Q000502:physiology; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D054371:Chemokine CXCL11; D018664:Interleukin-12
keywords: keratinocytes; leishmaniasis