High TARC plasma levels confer protection to long living individuals by inducing M2 profile

Cytokine. 2021 Jan:137:155305. doi: 10.1016/j.cyto.2020.155305. Epub 2020 Sep 29.

Abstract

A way to delay aging and the related low-grade chronic inflammatory state is to study the model of positive physiology such as the Long-Living Individuals (LLIs). Our recent studies have shown higher levels of the host defense BPI Fold-Containing Family B Member 4 (BPIFB4) protein in the LLIs' blood. Notably, BPIFB4 has been shown to influence monocytes typesetting and M2 anti-inflammatory phenotype (CD206+CD163++) macrophages skewing. According to the role of a complex cytokine milieu in guiding the macrophage polarization, here we found that circulating concentrations of thymus and activation regulated chemokine (TARC)/CCL17 and small-inducible cytokine B10 (IP-10)/CXCL10) cytokines, were additionally associated with the LLIs' state. In a differentiation process in vitro, the addition of LLIs' plasma to the cell culture medium, enhanced the ability of monocytes, either from LLIs or controls, to acquire a M2 phenotype. Interestingly, a neutralizing antibody against TARC blunted the M2 skewing effect of the LLIs' plasma. Collectively, these data indicate that exceptional longevity may associate with a peculiar anti-inflammatory myeloid profile responsible for improved reparative processes and reduced inflammatory status mediated in part by TARC and M2 generation.

Keywords: FACS; Longevity; M2 macrophages; Plasma profile; TARC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Chemokine CCL17 / blood*
  • Chemokine CXCL10 / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Longevity*
  • Macrophage Activation
  • Macrophages / classification
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Middle Aged

Substances

  • BPIFB4 protein, human
  • Chemokine CCL17
  • Chemokine CXCL10
  • Intercellular Signaling Peptides and Proteins