TY - JOUR
T1 - CD38⁺ endothelial remodeling marks spatially patterned vasculopathy in rapidly advancing periodontitis and peri-implantitis
AU - Easter, Quinn T.
AU - Huynh, Khoa L.A.
AU - Stolf, Camila Schmidt
AU - Xie, Jialiu
AU - Matuck, Bruno F.
AU - Hasuike, Akira
AU - Alvarado-Martinez, Zabdiel
AU - Kim, William S.
AU - Chen, Zhaoxu
AU - Ribeiro, Apoena Aguiar
AU - Pareek, Nivedita
AU - Azcarate-Peril, Andrea M.
AU - Wu, Di
AU - Casarin, Renato
AU - Ko, Kang I.
AU - Liu, Jinze
AU - Byrd, Kevin M.
N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/12
Y1 - 2026/12
N2 - Oral inflammatory diseases affect nearly half of all humans, yet mechanisms underlying rapidly-destructive inflammation remain poorly understood. We compared peri-implantitis with moderate- and high-grade periodontitis using integrated microbial and single-cell sequencing (>967,169-cells; single-cell RNA-seq, spatial proteotranscriptomics). Laser capture microdissection with compartmental microbiome analysis revealed reduced bacterial load and diversity in peri-implantitis. Expansion of the Human Periodontal Atlas with peri-implantitis single-cell RNA-seq data (36-samples; 121,395 cells) identified CD34+ vascular endothelial cell (VEC) rarefaction and oxidative stress, hypoxia, and NAD⁺ metabolism-associated transcriptional programs enriched in a TNFRSF6B⁺/ICAM1⁺ post-capillary venule (PC-VEC) subpopulation. NAD⁺-consuming ectoenzyme CD38 was selectively enriched and orthogonally confirmed by spatial transcriptomics (6-samples; 283,377-cells) and proteomics (23-samples; 562,397-cells). Spatial neighborhood analyses demonstrated CD38⁺-high PC-VEC expansion, closer proximity, and higher IL16–CD4 T cell signaling in peri-implantitis. Matched high-grade periodontitis biopsies confirmed spatially restricted CD38⁺-VECs despite similar microbial burden, identifying endothelial vasculopathy underlying rapidly advancing oral inflammation and a potential therapeutic axis.
AB - Oral inflammatory diseases affect nearly half of all humans, yet mechanisms underlying rapidly-destructive inflammation remain poorly understood. We compared peri-implantitis with moderate- and high-grade periodontitis using integrated microbial and single-cell sequencing (>967,169-cells; single-cell RNA-seq, spatial proteotranscriptomics). Laser capture microdissection with compartmental microbiome analysis revealed reduced bacterial load and diversity in peri-implantitis. Expansion of the Human Periodontal Atlas with peri-implantitis single-cell RNA-seq data (36-samples; 121,395 cells) identified CD34+ vascular endothelial cell (VEC) rarefaction and oxidative stress, hypoxia, and NAD⁺ metabolism-associated transcriptional programs enriched in a TNFRSF6B⁺/ICAM1⁺ post-capillary venule (PC-VEC) subpopulation. NAD⁺-consuming ectoenzyme CD38 was selectively enriched and orthogonally confirmed by spatial transcriptomics (6-samples; 283,377-cells) and proteomics (23-samples; 562,397-cells). Spatial neighborhood analyses demonstrated CD38⁺-high PC-VEC expansion, closer proximity, and higher IL16–CD4 T cell signaling in peri-implantitis. Matched high-grade periodontitis biopsies confirmed spatially restricted CD38⁺-VECs despite similar microbial burden, identifying endothelial vasculopathy underlying rapidly advancing oral inflammation and a potential therapeutic axis.
UR - https://www.scopus.com/pages/publications/105044537432
U2 - 10.1038/s41467-026-72452-2
DO - 10.1038/s41467-026-72452-2
M3 - Article
C2 - 42103720
AN - SCOPUS:105044537432
SN - 2041-1723
VL - 17
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6239
ER -