Role of macrophages/dendritic cells and NKT cell interaction in Th17 polarized chronic periodontitis

• Applicant: Professor Dr. Jean-Pierre Allam
• Subject Area: Dentistry, Oral Surgery
• Term: from 2008 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 58918792

Chronic periodontitis (CP) is an inflammatory condition of the periodontium. However, little is known about its pathophysiology. Obviously, antigen-presenting cells (APCs) like dendritic cells (DCs) or macrophages (Mo) are involved. In this context, we could demonstrate that in CP TLR4-positve Mo-like cells expressing Mo and DCs markers predominate. We could also detect in CP (i) a strong Th17 infiltrate (ii) that Mo-like cells produce Th17 propagating IL-23 and (iii) that in vitro generated Mo-like cells produce IL-23 upon TLR4 activation by CP-associated Porphyromonas gingivalis-LPS. Recent studies could detect Natural Killer T cells (NKTs) in CP but to date little is known about their inflammatory or regulatory role. Thus, we intend to characterize in CP (i) DC/Mo-like cells regarding structures for antigen recognition by NKTs (ii) phenotype of NKTs and their ability to produce IL-17 and (iii) their interaction with DC/Mo-like cells. Furthermore, we plan to analyze the involvement of NKTs in CP regarding TLR4 activation on APCs using an in vitro model. Following beneficial therapeutic use of topical calcineurin inhibitors (TCI) in atopic dermatitis we intend to investigate the impact of TCI on APCs and T cells involved in CP. The short-time aim is to further identify immunological mechanisms in CP. The long-time aim is to obtain a rational basis for specific therapeutic interventions using TCI.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 208: Aetiology and Sequelae of Periodontal Diseases - Genetic, Cell Biological and Biomechanical Aspects
• Participating Person: Professorin Dr. Natalija Novak