Patientenkolloquium 2019
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Project TP01





Investigators:
PD Dr. med. Jean-Pierre Allam
Department of Dermatology and Allergy
Medical Faculty
University of Bonn

Prof. Dr. med. Natalija Novak
Department of Dermatology and Allergy
Medical Faculty
University of Bonn



First Funding Period

Role of distinct oral mucosal dendritic cell subsets in the pathophysiology of chronic periodontitis

Summary
Chronic periodontitis (CP) is an inflammatory condition of the periodontium, which affects over 70% of the adult population and represents the major cause for tooth loss. Since only little is known about its pathophysiology, to date therapy of CP is restricted to unspecific interventions such as improvement of oral hygiene, topical application of antimicrobial substances, or systemic administration of antibiotics. Hence, elucidating the underlying immunological mechanisms leading to the initiation and chronic manifestation of CP might give rise to new and more specific therapeutic strategies. Without any doubt, antigen-presenting cells (APC) such as dendritic cells (DCs) are involved in the pathogenesis of CP and different immunological mechanisms contribute to the initial and chronic phase of CP. While Porphyromonas gingivalis (PG) as a major pathogen in CP is most likely involved in the initial phase of the disease there is convincing evidence that during chronic manifestation, a subgroup of CP is associated with auto-antibodies to gingival antigens suggesting an underlying autoimmune reaction.
The short-time aim is to identify immunological mechanisms critical not only for the initiation but also for the chronic manifestation as well as the induction of autoimmunity in CP. The long-time aim is to elucidate critical steps in the pathophysiology of CP, which might be targeted by specific therapeutic interventions leading to the prevention of chronification and autoimmune induction. Moreover, in view of treatments using the oral route as an application site such as sublingual immunotherapy (SLIT) or other oral vaccines, knowledge about immune mechanisms leading to induction of TH17 and autoimmunity within the oral mucosa might impact on the development of new vaccination strategies or selection of adjuvants.


Poster




Second Funding Period

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

Summary
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.