ABSTRACT
BACKGROUND: Despite high bacterial colonization, acute infections are rare in the oral mucosa, implicating tolerogenic predominance. Bacterial antigens like LPSs are recognized by innate immunity receptors such as Toll-like receptor 4 (TLR4), associated with LPS receptor (CD14). OBJECTIVES: Toll-like receptor 4 agonist monosphoryl lipid A has been successfully used as adjuvant in subcutaneous immunotherapy, suggesting reinforcement of allergen-specific tolerance. Recently sublingual immunotherapy (SLIT) has been shown to be an effective alternative to subcutaneous immunotherapy. We observed CD14 expression on human oral Langerhans cells (oLCs), representing a major target of SLIT. However, not much is known about TLR4 expression and its effect on oLCs. METHODS: Cell suspensions were obtained by trypsinization of human oral mucosa and analyzed by flow cytometry, RT-PCR, cytometric bead arrays, ELISA, and mixed lymphocyte reactions. RESULTS: We could show that oLCs express TLR4, and its ligation by monosphoryl lipid A upregulated expression of coinhibitory molecules B7-H1 and B7-H3 while surface expression of costimulatory molecule CD86 was concomitantly decreased. Furthermore, TLR4 ligation on oLCs increased their release of the anti-inflammatory cytokine IL-10 and decreased their stimulatory capacity toward T cells. Moreover, TLR4-ligation on oLCs induced IL-10, TGF-beta1, Forkhead box protein 3, IFN-gamma, and IL-2 production in T cells. CONCLUSION: In view of these data, TLR4-ligation on oLCs might not only play a role in pathogen recognition for efficient immunity but also contribute to the tolerogenic state predominating in the oral cavity.
Subject(s)
Adjuvants, Immunologic/pharmacology , Immune Tolerance/drug effects , Langerhans Cells/immunology , Lipid A/analogs & derivatives , Mouth Mucosa/immunology , Toll-Like Receptor 4/antagonists & inhibitors , Antigens, CD/metabolism , B7 Antigens , B7-2 Antigen/metabolism , B7-H1 Antigen , Cytokines/metabolism , Down-Regulation , Forkhead Transcription Factors/metabolism , Humans , In Vitro Techniques , Interleukin-10/metabolism , Langerhans Cells/metabolism , Lipid A/pharmacology , Mouth Mucosa/metabolism , Receptors, Immunologic/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Th1 Cells/metabolism , Toll-Like Receptor 4/metabolism , Transforming Growth Factor beta1/metabolism , Up-RegulationABSTRACT
Objective. The primary diagnosis of synovial chondromatosis of the temporomandibular joint is extremely rare. Often many months, or even years pass before the diagnosis is confirmed. Study Design. Eight patients with synovial chondromatosis were treated by arthrotomy. In addition to the definitive diagnosis, histologic classification according to the stages proposed by Milgram was undertaken and confirmed with the literature. Results. The predominant symptoms of synovial chondromatosis, including pain, swelling, restricted movement of the mandible, and crepitation, were evaluated. Nevertheless, more than 80% of the patients were previously primarily treated on the basis of other tentative diagnoses. Conclusion. Synovial chondromatosis of the temporomandibular joint should be included in the differential diagnosis of chronic swelling and pain in the preauricular region, and the patient should be sent for appropriate diagnostics and therapy at an early stage.
