Age-associated T cell immunity decreases circulating endothelial progenitor cells.

Fang Zhang, Qiuchen Zhao, Shuzhen Guo, Gen Hamanaka, Dong-Bin Back, Shin Ishikane, Ester Licastro, Ji-Hyun Park, Wenlu Li, Elga Esposito, Ksenia V Kastanenka, Brian J Bacskai, Kazuhide Hayakawa

Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA. · pubmed

Paper

Abstract

A reduction in circulating endothelial progenitor cells (EPCs) comprise an important part of vascular aging. However, the underlying mechanisms that mediate this EPC decline remain unclear. Here, we demonstrate a novel molecular mechanism where aging increases inhibitory T cell subsets and impairs SDF1-mediated increase of circulating EPCs. SomaScan proteomics and western blot analysis revealed FABP4 as the top upregulated protein in plasma and was also increased in the bone marrow in aging. Importantly, treatment with FABP4 in bone marrow cells increased inhibitory T cells while decreased SDF-1 receptor, CXCR4 in EPCs, whereas blocking FABP4 signaling by BMS309403 or depleting these T cells restored surface expression of CXCR4 in EPCs. Notably, FABP4-mediated decrease of circulating EPC in aging were restored by therapeutic administration of mitochondria, wherein plasma FABP4 was decreased along with reducing inhibitory T cell induction in bone marrow and increasing circulating EPCs in older mice. Collectively, these findings provide new insight into the involvement of age-associated T cell immunity in EPC dysregulation, and FABP4 may be a therapeutic target to detain vascular aging.

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Research summary

The paper claims that age-associated T cell immunity impairs the increase of circulating endothelial progenitor cells through a mechanism involving FABP4. This research addresses a potential root cause of vascular aging, linking immune system changes to the decline in endothelial progenitor cells, which is relevant to understanding and potentially mitigating aspects of aging.

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