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Journal of Dental Research
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Dendritic Cells at the Oral Mucosal Interface

C.W. Cutler1,* and R. Jotwani2

1 Department of Periodontics, 110 Rockland Hall, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8703, USA; and
2 Periodontal Molecular Immunology Laboratory, Department of Periodontics, Stony Brook School of Dental Medicine


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  		Figure. Oral lymphoid foci (OLF): local site for induction of immunity vs. tolerance? Analysis of inter-papillary tissue in chronic adult periodontitis (CAP) reveals an organizational structure that we have termed OLF. OLF consist of: (i) Langerhans cells (LC) and {gamma}{delta} T-cells in the epithelium, with double-positive maturing CD1a+CD83+ LC just under the basement lamina; (ii) dermal dendritic cells (DDC) and macrophages infiltrate the lamina propria, with double-positive dendritic-cell-specific ICAM-3-grabbing non-integrins (DC-SIGN + CD83 + dermal dendritic cells (DDC) deeper within the lamina propria; (iii) immune conjugates are formed in the lamina propria, consisting of CD83+DC and B-cells and naïve and memory CD4+ T-cells; (iv) plasma cells infiltrate the lamina propria, while polymorphonuclear leukocytes (PMN) migrate through and out of the gingival crevice. Shown is the ability of P. gingivalis and its pathogen-associated molecular patterns (PAMPs) (e.g., lipopolysaccharide [LPS], fimbriae [fim]) to invade the gingival/pocket epithelium and gain access to LC. Toll-like receptors (TLRs) and C-type lectin receptors (CTLRs) expressed by DDCs play counter-regulatory roles in responses to bacteria, their PAMPs. TLRs stimulate DC activation, leading to expression of co-stimulatory molecules (CD40, CD80, CD86), maturation (CD83), and secretion of IL-12, TNF{alpha}, all of which favor a Th1 effector response. CTLRs function specifically to take up bacteria and self-antigen (Ag), but lack Toll-Interleukin-1R (TIR) activation domains for DC maturation and cytokine secretion, thus favoring a Th2 or regulatory (Treg) response. The cross-talk between TLR and CTLRs is a ’toggle switch’ between immunity and tolerance.

 

Journal of Dental Research, Vol. 85, No. 8, 678-689 (2006)
DOI: 10.1177/154405910608500801
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