Recruitment of inflammatory monocytes by senescent fibroblasts inhibits antigen-specific tissue immunity during human aging

Emma S Chambers, Milica Vukmanovic-Stejic, Barbara Shih, Hugh Trahair, Priya Subramanian , Oliver P. Devine , James Glanville , Derek W. Gilroy, Malcolm Rustin , Thomas C Freeman, Neil Mabbott, Arne N Akbar

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously shown that healthy older adults exhibit reduced cutaneous immune responses during a varicella zoster virus (VZV) antigen challenge that correlated with a non specific inflammatory response to the injection itself.
Here we found that needle damage during intradermal injections in older adults led to an increase in the number of cutaneous senescent fibroblasts expressing CCL2, resulting in the local recruitment of inflammatory monocytes. These infiltrating monocytes secreted prostaglandin E2 (PGE2) that inhibited resident memory T cell (TRM) activation and proliferation. Pre-treatment of older subjects with a p38-MAPK inhibitor in vivo decreased CCL2 expression and inhibited monocyte recruitment and secretion of PGE2. This coincided with an increased response to VZV antigen challenge in the skin. Our results point to a series of molecular and cellular mechanisms that link cellularsenescence, tissue damage, excessive inflammation and reduced immune responsiveness
in human skin and demonstrate that tissue-specific immunity can be restored in older adults by the short-term inhibition of inflammatory responses.
Original languageEnglish
JournalNature Aging
DOIs
Publication statusPublished - 14 Jan 2021

Fingerprint

Dive into the research topics of 'Recruitment of inflammatory monocytes by senescent fibroblasts inhibits antigen-specific tissue immunity during human aging'. Together they form a unique fingerprint.

Cite this