Kidney inflammaging is promoted by CCR2+ macrophages and tissue-derived micro-environmental factors

Cell Mol Life Sci. 2021 Apr;78(7):3485-3501. doi: 10.1007/s00018-020-03719-0. Epub 2020 Dec 12.


The incidence of disorders associated with low inflammatory state, such as chronic kidney disease, increases in the elderly. The accumulation of senescent cells during aging and the senescence-associated secretory phenotype, which leads to inflammaging, is known to be deleterious and account for progressive organ dysfunction. To date, the cellular actors implicated in chronic inflammation in the kidney during aging are still not well characterized. Using the DECyt method, based on hierarchical clustering of flow cytometry data, we showed that aging was associated with significant changes in stromal cell diversity in the kidney. In particular, we identified two cell populations up-regulated with aging, the mesenchymal stromal cell subset (kMSC) expressing CD73 and the monocyte-derived Ly6C+ CCR2+ macrophage subset expressing pro-inflammatory cytokines. Aged CD73+ kMSCs depicted senescence associated features with low proliferation rate, increased DNA damage foci and Ccl2 expression. Using co-cultures experiments, we showed that aged CD73+ kMSC promoted monocyte activation and secretion of inflammatory cytokines albeit less efficiently than young CD73+ kMSCs. In the context of ageing, increased frequency of CD73+ kMSC subpopulations could provide additional niche factors to newly recruited monocytes favoring a positive regulatory loop in response to local inflammation. Interfering with such partnership during aging could be a valuable approach to regulate kidney inflammaging and to limit the risk of developing chronic kidney disease in the elderly.

Keywords: Aging; CCR2; CD73; Inflammaging; Kidney; Macrophages; Mesenchymal stromal cells; Senescence.

MeSH terms

  • Animals
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / metabolism
  • Cellular Microenvironment / immunology*
  • Cellular Senescence / immunology*
  • Cytokines / metabolism
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Kidney / immunology*
  • Kidney / metabolism
  • Kidney / pathology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / pathology
  • Receptors, CCR2 / metabolism*


  • CX3C Chemokine Receptor 1
  • Ccr2 protein, mouse
  • Cx3cr1 protein, mouse
  • Cytokines
  • Receptors, CCR2