Neutrophil subtypes and periodontal disease; impact of serine proteases

Neutrophils are critical components of inflammation and increasingly recognized as a heterogeneous cell type with multiple distinct subtypes simultaneously present in circulation. It is unclear if subtypes differ functionally, but the proportion of subtypes differs in certain diseases.

One such is periodontitis, i.e., inflammation-driven destruction of periodontal ligaments and bone where normal neutrophil presence/function is key to avoid disease.

One aim is to characterize neutrophil subtypes with the hypothesis that certain subtypes have increased potential to fine-tune inflammation and steer it away from becoming destructive (as in periodontitis).By studying genetic neutrophil defects associated with periodontitis, one can get clues as to what functions are critical for periodontal health.

Surprisingly, one factor is neutrophil serine proteases (NSPs). NSPs are proteolytic enzymes commonly thought to worsen destruction by their ability to degrade matrix proteins.

On the contrary, the clinical reality of individuals lacking NSP activity feature exceptionally aggressive periodontitis. Thus, one mechanism neutrophils use to dampen destructive inflammation is mediated by NSP activity.

I hypothesize that NSPs dampen destructive inflammation by degrading cytokines and growth factors that would otherwise drive disease.The project will increase knowledge on destructive inflammation in periodontitis, but may also provide insights into regulation of inflammation in general.