Characterisation of salivary gland macrophages during development, homeostasis, and repair

Abstract

Every year over 500,000 people are diagnosed with head and neck cancer, and the current treatment regime relies on targeted radiotherapy, which inadvertently also damages the salivary glands. Following irradiation, salivary gland injury is often defined by inflammatory cell infiltration; however, this has been poorly characterised.

Macrophages are mononuclear innate immune cells which have become of increasing interest in the study of regeneration, as their non-classical functions have been elucidated, in addition to their classical inflammatory functions. Macrophages can regulate tissue clearance, by mounting or reducing inflammatory responses, and can have direct communication with stem cells to drive development and regeneration. To assess the potential role of these cells in the pathology and repair of salivary glands, I have characterised their expression, subgroups, lifespan, turnover, origin, development, and response to injury for the first time.

This data showed that macrophages are embryonically seeded, like many other well-studied tissues, and are replaced by definitive progenitors after weaning. I also demonstrate that these cells are radioresistant, long lived and only significantly replenished by monocytes following radiation injury longer term, compared to steady state. I also demonstrated for the first time that there is a distinct and significant sex difference within the immune compartment of the salivary glands. Collectively, this expands our understanding of macrophages in salivary gland regeneration, which will undoubtedly lead to the discovery of therapeutic targets to promote regeneration after irradiation injury.