The same inflammatory immune cell subgroup expands more than 10-fold in the lungs of healthy older mice, monkeys and humans and sustains chronic inflammation
The same inflammatory immune cell subgroup expands more than 10-fold in the lungs of healthy older mice, monkeys and humans and sustains chronic inflammation
Researchers at Texas Biomedical Research Institute compared alveolar macrophages in young and older mice, baboons and humans. These immune cells patrol the lung’s air sacs, clearing dust, microbes and dead cells. In all three species, the same subgroup of cells with signs of chronic inflammation expanded more than 10-fold with age. Experiments in mice showed that two processes contribute to this expansion: some macrophages already in the lungs change their phenotype, while new cells enter from the blood through a process that requires the receptor CCR2. The study was published on 7 October 2026 in Nature Communications.
The authors compared mice, baboons and humans to assess how widely this process of lung aging is shared across mammals. In 18-month-old mice (an advanced age for mice), baboons older than 15 years and humans older than 60 years, the proinflammatory subgroup accounts for at least ten times the proportion of all macrophages seen in three-month-old mice, young baboons and adults aged 20 to 45 years. In all three species, these cells express higher levels of the receptors CCR2 and Fas (CD95). This receptor combination distinguishes cells that have recently arrived from the blood from resident macrophages that live in the lungs for years.
Larry Schlesinger and Susanta Pahari’s team at Texas Biomedical Research Institute conducted experiments in mice to distinguish the two sources of this subgroup. First, they depleted alveolar macrophages in young and old mice and transferred labeled cells from young donors into their lungs. Within two days, 30 to 40% of the transferred cells in old lungs had acquired the same proinflammatory phenotype, showing that the aged lung tissue itself induces this phenotype in cells placed there. The authors then injected labeled monocytes (macrophage precursors) into the bloodstream and found that they populated the lungs of old mice but rarely entered those of young mice. Monocytes lacking CCR2 remained in the blood and entered the lungs of neither young nor old mice, showing that this receptor was required for entry.
The recruited cells are short-lived: their numbers peak on the fifth day after injection and then gradually decline, while resident macrophage numbers remain stable throughout the ten-day observation period. The recruited cells express increasing levels of Fas. When the authors administered an antibody that blocks its binding partner FasL, the recruited cells survived longer, and levels of the inflammatory protein TNF in lung fluid fell. Cell death proceeds through caspase-8 and caspases-3/7, components of the extrinsic pathway of programmed cell death. Together, these findings describe a self-sustaining cycle: aged tissue recruits new cells through CCR2, the cells rapidly undergo Fas-mediated death, and further incoming cells replace them, sustaining inflammation.
The same laboratory first identified this subgroup in old mice in 2019 and linked it to their reduced ability to control tuberculosis infection. The chronic, low-grade inflammation associated with healthy aging is called inflammaging. Immunologist Claudio Franceschi introduced the term in 2000, and it has since become a central concept in aging research. The new study identifies two specific mechanisms contributing to this process: CCR2-mediated recruitment and Fas-mediated apoptosis.
The authors plan to test directly whether this mechanism contributes to older individuals’ reduced ability to resist respiratory infections. CCR2 and Fas are already being discussed as potential targets for future interventions.