title: IL-10 suppresses IL-17-mediated dermal inflammation and reduces the systemic burden of Vaccinia virus in a mouse model of eczema vaccinatum.
abstract: Individuals with atopic dermatitis (AD) are susceptible to a severe, potentially fatal, systemic infection and inflammatory response following exposure to Vaccinia virus (VV). IL-10 acts both as an inducer of Th2 responses and as a regulator of T cell activation. It has been shown to limit skin inflammation elicited by contact sensitizers. AD exacerbations have been associated with decreased IL-10 function. We used IL-10(-/-) mice to test the role of the cytokine in VV immunity. They exhibited larger primary lesions and increased cutaneous neutrophil infiltration compared to wild-type (WT) counterparts. This was associated with enhanced production of IL-17A, IL-17F and CXCL2. Paradoxically, despite intact adaptive immune responses, tissue viral burdens were increased in IL-10(-/-) mice. These findings suggest that IL-10 is important in limiting skin inflammation induced by VV and that abnormal IL-17-driven neutrophil recruitment at the primary infection site in the skin results in increased systemic viral dissemination.
authors.affiliation: Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Alanna R
authors.initials: AR
authors.lastname: Darling
authors.affiliation: Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Eva-Jasmin
authors.initials: EJ
authors.lastname: Freyschmidt
authors.affiliation: Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Burton
authors.affiliation: Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Koleoglou
authors.affiliation: Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Michiko K
authors.initials: MK
authors.lastname: Oyoshi
authors.affiliation: Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: hans.oettgen@childrens.harvard.edu.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Oettgen
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007617:Kaposi Varicelliform Eruption / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D019562:Viral Load
chemical_list: D020381:Interleukin-17; D016753:Interleukin-10
keywords: Atopic dermatitis; Eczema vaccinatum; Vaccine