Single‐cell sequencing identifies inflammation‐promoting fibroblast–neutrophil interaction in peri‐implantitis

Abstract

AimTo reveal the cellular composition and molecular environment of the periodontal and peri‐implant inflammatory infiltrates through a single‐cell sequencing technique, which may explain the pathological difference between these two diseases. A special focus was placed on the phenotypes and potential roles of neutrophils and fibroblasts in peri‐implant/periodontal tissue immunity.Materials and MethodsHigh‐throughput single‐cell transcriptomic profiling of peri‐implant tissues from patients with peri‐implantitis as well as periodontal tissues from patients with periodontitis and healthy donors was performed. Immunofluorescence analysis was carried out to further validate the identified cell subtypes and their involvement in peri‐implantitis and periodontitis.ResultsBased on our single‐cell resolution analysis, a quantified proportional increase of neutrophil (Neu) subtypes was shown in peri‐implantitis. Among these, a predominance of Neutro_CXCR2 was revealed. We also found the involvement of inflammation‐promoting fibroblasts as well as a predominance of CXCL8+ fibroblast–CXCR2+ neutrophil interaction in peri‐implantitis.ConclusionsOur study indicated that the predominance of CXCL8+ fibroblast–CXCR2+ neutrophil interaction might underline the enhanced host response in peri‐implantitis compared with periodontitis. This information offers a molecular basis by which fibroblast and neutrophil subtypes might be diagnostically and therapeutically targeted in peri‐implantitis.

Biological Response of the Peri-Implant Mucosa to Different Definitive Implant Rehabilitation Materials

“…An increase of polymorphonuclear leukocytes (PMN) in peri-implant tissue is considered a significant indicator of inflammation, which could lead to mucositis and peri-implantitis (Berglundh et al, 2018; Schwarz et al, 2018). A single-cell sequencing study supports the involvement of PMNs in inflammation, as it has shown elevated levels of CXCL8, a PMN-attracting cytokine, in peri-implant tissue [ 31 ]. Therefore, the presence of PMNs and their association with inflammation could indicate an association with the pathogenesis of peri-implant diseases [ 32 , 33 ].…”

Platelet-Rich Fibrin Increases CXCL8 Expression in Gingival Fibroblasts

“…CXCL8 is more than an inflammatory cytokine, as it is expressed in healthy periodontal tissues, suggesting its involvement in the permanent need for the periodontium to defend against the microbial burden of the oral cavity [ 10 ]. Moreover, once homeostasis shifts into the pathological stage, CXCL8 becomes a marker of periodontitis [ 8 , 9 , 10 ] and periimplantitis [ 11 ]. The fibroblasts are the primary producers of CXCL8 in periodontitis tissues [ 10 ].…”

“…CXCL8 expression is a double-edged sword: (i) it supports local immunity being constantly expressed at a low level, (ii) or at transient higher levels during wound healing, (iii) however, when chronically expressed at high levels, CXCL8 becomes a key mediator associated with pathological inflammation and overaccentuated neutrophil recruitment and degranulation, overall causing tissue damage [ 7 ]. It is, therefore, not surprising that in healthy periodontal tissues, CXCL8 is regularly expressed to control tissue homeostasis, but CXCL8 is increasingly expressed in the pathological conditions of periodontitis [ 8 , 9 , 10 ] and periimplantitis [ 11 ]. Importantly, evidence suggests that fibroblasts are the primary source of CXCL8 in periodontitis [ 10 ] and periimplantitis [ 11 ].…”

“…It is, therefore, not surprising that in healthy periodontal tissues, CXCL8 is regularly expressed to control tissue homeostasis, but CXCL8 is increasingly expressed in the pathological conditions of periodontitis [ 8 , 9 , 10 ] and periimplantitis [ 11 ]. Importantly, evidence suggests that fibroblasts are the primary source of CXCL8 in periodontitis [ 10 ] and periimplantitis [ 11 ]. Thus, CXCL8 became a significant target of in vitro research in an overall attempt to understand its regulation in gingival fibroblasts.…”