Archives of Dermatological Research

, Volume 306, Issue 2, pp 143–155 | Cite as

Mice with heterozygous deficiency of manganese superoxide dismutase (SOD2) have a skin immune system with features of “inflamm-aging”

  • J. Scheurmann
  • N. Treiber
  • C. Weber
  • A. C. Renkl
  • D. Frenzel
  • F. Trenz-Buback
  • A. Rueß
  • G. Schulz
  • K. Scharffetter-Kochanek
  • J. M. Weiss
Original Paper

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.

Keywords

Dendritic cells Inflamm-aging Manganese superoxide dismutase Aging T cells 

Abbreviations

CHS

Contact hypersensitivity

DC

Dendritic cells

LC

Langerhans cells

SOD2

Manganese superoxide dismutase

TNCB

2,4,6-Trinitrochlorobenzene

LPS

Lipopolysaccharide

SEA

Staphylococcal enterotoxin A

Notes

Acknowledgments

This work was supported by a grant from the German Research Foundation: Clinical Research Group KFO 142 ‘‘Molecular and Cellular Aging—From Mechanisms to Clinical Perspectives’’ and Grant WE1919/5-1 to JMW. We thank M. Kohn for his help with breeding of the SOD2 heterozygous mice.

Conflict of interest

The authors state no conflict of interest.

Supplementary material

403_2013_1389_Fig1_ESM.jpg (743 kb)

Supplementary figure for review

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • J. Scheurmann
    • 1
  • N. Treiber
    • 1
  • C. Weber
    • 1
  • A. C. Renkl
    • 1
  • D. Frenzel
    • 1
  • F. Trenz-Buback
    • 1
  • A. Rueß
    • 1
  • G. Schulz
    • 1
  • K. Scharffetter-Kochanek
    • 1
  • J. M. Weiss
    • 1
  1. 1.Department of Dermatology and AllergologyUniversity of UlmUlmGermany

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