title: Mice with heterozygous deficiency of manganese superoxide dismutase (SOD2) have a skin immune system with features of "inflamm-aging".
abstract: Dendritic cells (DC) are central in regulating skin immunity. Immunosenescence is associated with a chronic inflammatory state. Little is known about the contribution of DC to "inflamm-aging". When determining langerhans cell (LC) numbers, we found a 60 % reduction of LC in aged epidermis. Reactive oxygen species(ROS) are linked with aging. The mitochondrial manganese superoxide dismutase (SOD2) is in the first line of antioxidant defense. We investigated the function of DC from SOD2 heterozygous mice (SOD2+/-) and found that at 4 months of age LC numbers are not altered, but activated LC have impaired expression of MHC-II and CD44. Immature SOD2+/- DC produced increased proinflammatory IL-6 and chemokines CXCL1 and CXCL2. Upon challenge SOD2+/- DC accumulated ROS. When activating SOD2+/- DC by LPS they less efficiently upregulated MHC-II, CD86 and CD44. Surprisingly, in vivo contact hypersensitivity (CHS) was enhanced in SOD2+/- mice although SOD2+/- DC were less potent in stimulating wt T cells. However, SOD2+/- T cells showed increased proliferation, even when stimulated with SOD2+/- DC, possibly explaining the increased CHS. Our findings suggest that SOD2 is a molecular candidate in the regulation of "inflamm-aging" conveying both immunosuppressive and proinflammatory signals through alteration of DC and T cell functions.
authors.affiliation: Department of Dermatology and Allergology, University of Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Scheurmann
authors.forename: N
authors.initials: N
authors.lastname: Treiber
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.forename: A C
authors.initials: AC
authors.lastname: Renkl
authors.forename: D
authors.initials: D
authors.lastname: Frenzel
authors.forename: F
authors.initials: F
authors.lastname: Trenz-Buback
authors.forename: A
authors.initials: A
authors.lastname: Ruess
authors.forename: G
authors.initials: G
authors.lastname: Schulz
authors.forename: K
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.forename: J M
authors.initials: JM
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology*; D006579:Heterozygote; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D051940:B7-2 Antigen; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase