The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence.

Siew Min Ong, Eva Hadadi, Truong-Minh Dang, Wei Hseun Yeap, Crystal Tze-Ying Tan, Tze-Pin Ng, Anis Larbi, Siew Cheng Wong

Onderzoeksoutput: Articlepeer review

130 Citaten (Scopus)

Samenvatting

Human primary monocytes comprise a heterogeneous population that can be classified into three subsets based on CD14 and CD16 expression: classical (CD14high/CD16−), intermediate (CD14high/CD16+), and non-classical (CD14low/CD16+). The non-classical monocytes are the most pro-inflammatory in response to TLR stimulation in vitro, yet they express a remarkably high basal level of miR-146a, a microRNA known to negatively regulate the TLR pathway. This concurrence of a pro-inflammatory status and a high miR-146a level has been associated with cellular senescence in other cell types. Hence, we assessed the three monocyte subsets for evidence of senescence, including proliferative status, telomere length, cellular ROS levels, and mitochondrial membrane potential. Indeed, the non-classical subset exhibited the clearest hallmarks of senescence, followed by the intermediate and then the classical subset. In addition, the non-classical subset secreted pro-inflammatory cytokines basally in vitro. The highly pro-inflammatory nature of the non-classical monocytes could be a manifestation of the senescence-associated secretory phenotype (SASP), likely induced by a high basal NF-κB activity and IL-1α production. Finally, we observed an accumulation of the non-classical monocytes, in conjunction with higher levels of plasma TNF-α and IL-8, in the elderly. These factors may contribute to inflamm-aging and age-related inflammatory conditions, such as atherosclerosis and osteoarthritis. With our new understanding that the non-classical monocyte subset is a senescent population, we can now re-examine the role of this subset in disease conditions where this subset expands.
Vertaalde titel van de bijdrageThe pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence.
Originele taal-2English
TijdschriftCell & Death Disease
Volume9
DOI's
StatusPublished - feb 2018
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence.'. Samen vormen ze een unieke vingerafdruk.

Citeer dit