The Th17/Treg balance is disturbed during aging

Exp Gerontol. 2013 Dec;48(12):1379-86. doi: 10.1016/j.exger.2013.09.003. Epub 2013 Sep 20.

Abstract

Aging is associated with multiple changes in the proliferative and functional abilities of the immune system which are not related to any pathology but consequences in immunosenescence and inflammaging. T helper (TH) 17 cells have been implicated in the development of autoimmune and chronic inflammatory diseases in humans. Additionally, a reciprocal relationship between these pro-inflammatory TH17 and the anti-inflammatory regulatory T cells (Tregs) has been described. Recent studies reported an increase of TH17 cells in aged humans and aged mice, but the role of TH17 cells and their relation to Tregs is poorly understood in human aging. This study investigated the proportion of TH17 (CD4+ IL23 receptor(R)+) cells and Tregs (CD4+ Foxp3+) as well as Interleukin (IL)-17 and IL-10 production in four different age groups from human healthy donors. The data revealed a continual increase of basal CD4+ IL23R+ cell amounts in the different age groups. By analyzing the balance of both T-cell subsets it was observed that, on a basal resting level, TH17 cells were significantly increased in older individuals whereas Tregs were reduced. However, the TH17/Treg ratio decreased age-dependently after stimulation and was accompanied by elevated Foxp3 mRNA and IL-10 protein expressions. In conclusion, changes of the TH17/Treg ratios in combination with altered cytokine expression during aging may contribute to an imbalance between the pro-inflammatory and the anti-inflammatory immune response. This indicates a higher susceptibility to develop inflammatory diseases with increasing age.

Keywords: Aging; Foxp3; IL-10; IL-17; Th17; Treg.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Aging / metabolism
  • Cells, Cultured
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Healthy Volunteers
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Phenotype
  • Phytohemagglutinins / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Young Adult

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL10 protein, human
  • IL23R protein, human
  • Inflammation Mediators
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Phytohemagglutinins
  • RNA, Messenger
  • RORC protein, human
  • Receptors, Interleukin
  • Interleukin-10