Tissue Specification of Neutrophil States at the Gingival Barrier
Objectives: Neutrophils are essential for maintaining gingival health, yet exaggerated neutrophil recruitment and activation drive the pathogenesis of periodontitis. Given these critical but divergent roles, we aimed to characterize gingival neutrophil subsets in homeostasis and during experimental periodontitis. Methods: Ligature-induced periodontitis (LIP) was performed in C57Bl/6 mice according to an approved NIDCR animal protocol. Gingiva and circulating blood were harvested at steady state and during distinct timepoints during LIP, and gingiva was subjected to gentle enzymatic digestion. Single cell suspensions were analyzed with single-cell RNA-sequencing (scRNA-seq) and full spectrum flow cytometry. Results: Gingival neutrophils showed a spectrum of maturation states during homeostasis. LIP induced a temporary elevation in circulating immature neutrophils and instigated multiple, asynchronous increases in neutrophil numbers within the gingiva. Transcriptomic and proteomic analysis indicated that neutrophils in the gingiva acquired distinct states relative to circulating neutrophils, and pre-neutrophil and immature neutrophil populations persisted within the gingiva during health and disease. Conclusions: Gingival neutrophil populations with diverse signatures are present in health and expand during experimental periodontitis. The presence of distinct transcriptional and proteomic gingival neutrophil states suggests that neutrophil subsets with distinct functionality may play specific roles at the gingival barrier.
2024 IADR/AADOCR/CADR General Session (New Orleans, Louisiana) New Orleans, Louisiana
2024 0065 Periodontal Research-Pathogenesis
Fraser, David
( National Institute of Dental and Craniofacial Research, National Institutes of Health
, Washington
, Maryland
, United States
)
Kelly, Michael
( Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Healt
, Frederick
, Maryland
, United States
)
Moutsopoulos, Niki
( National Institute of Dental and Craniofacial Research, National Institutes of Health
, Washington
, Maryland
, United States
)
NIH/NIDCR Intramural Funding
NONE
Oral Session
Inflammatory Immune Response in Periodontal Health and Disease
Wednesday,
03/13/2024
, 08:30AM - 10:00AM