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. 2022 Dec 22;14:1041333. doi: 10.3389/fnagi.2022.1041333

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Copyright © 2022 Bui, Jickling and Winship.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Neutrophil phenotypic differentiation during circulation and neutrophil phenotypic heterogeneity in aging. (A) Immature neutrophils are produced in the bone marrow, where they express either CXCR4 and CD62L on the cell surface to remain in the bone marrow or CXCR2 to be released into circulation as mature neutrophils. Aged neutrophils, after completing their immune functions in the circulation, have an increased expression of CXCR4 and a decreased expression of CXCR2 and CD62L to prompt their return to the bone marrow. (B) During organismal aging, circulating neutrophils demonstrated phenotypic changes compared to those in young individuals. Circulating neutrophils in aged individuals are hyperactive, having decreased CXCR4 and CD44 expression that diminish their efferocytosis and clearance. They also express high levels of CXCR1, CXCL1, and CXCL12 to help them remain in circulation, thus, creating a pro-inflammatory microenvironment. This condition of inflammaging makes aged individuals more susceptible to inflammatory stimuli.