Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus

Abstract

Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease that targets stratified epithelia, including those lining the oral cavity. The intraoral variant of LP (OLP) is associated with interferon (IFN)-γ production by infiltrating T lymphocytes; however, the role of epithelial cells in the etiopathogenesis OLP is not completely understood. There is however a growing body of evidence regarding the involvement of epithelial-derived cytokines, immune receptors, and costimulatory molecules in the pathobiological processes that promote and sustain OLP. In the present study, we used a reverse transcriptase-polymerase chain reaction assay to assess whether CD40-a receptor found mainly on antigen presenting cells-and the costimulatory molecule CD86 were expressed in oral keratinocytes (three strains of primary normal oral keratinocytes and the H357 cell line) in the presence or absence of IFN-γ. To further characterize the involvement of CD40 in OLP, expression and distribution of receptor and ligand (CD40/CD154) in tissues from OLP were evaluated by immunohistochemistry. The present results are the first to show that both CD40 and CD86 are constitutively expressed at low levels in oral keratinocytes and that their expression was enhanced by IFN-γ stimulation. The intensity of CD40 staining in OLP tissues was strong. Taken together, the results strongly suggest that CD40 and CD86 play a role in the pathophysiology of oral inflammatory diseases such as OLP.

The immunopathogenesis of oral lichen planus—Is there a role for mucosal associated invariant T cells?

“…30 Overall, the results of this study strongly suggest that CD40 and CD86 may play an important pathophysiologic role in oral inflammatory diseases like OLP. 30 Moreover, a recent study assessed the production of keratinocyte-derived CXCL9/10/11 under basal and inflammatory conditions as well as the role these chemokines may play in the pathogenesis of OLP. 31 This study showed that tissues from OLP patients harboured significantly higher levels of CXCL9/10/11 compared to normal oral mucosa demonstrating that normal oral keratinocytes have the ability to produce chemotactic molecules and mediate T-cell recruitment.…”

“…IHC was used to further evaluate the involvement of CD40 in OLP with results showing strong intensity of CD40 staining in OLP tissues . Overall, the results of this study strongly suggest that CD40 and CD86 may play an important pathophysiologic role in oral inflammatory diseases like OLP …”

“…Cytokines produced by immune cells that can act as signalling molecules and induce chemotaxis • OLP has shown significantly higher levels of CXCL9/10/11 • Oral keratinocytes can produce these chemokines CXCL9/10/11 • CXCL9/10/11 are specific for CXCR3 and CCL5, the ligand for CCR5 • CCR5 and CXCR3 are selectively expressed on Th1 T cells • CXCL9 and 10 production, in particular CXCL9 production, by oral keratinocytes can be upregulated following inflammatory and infectious exposure • Production of these molecules by oral keratinocytes may mediate a T-cell inflammatory response 27,30,32 Interleukins Cytokines with the primary function of modulating cellular behaviour • Significantly decreased tendency for IL-2 has been shown in erosive and reticular OLP, while a significantly increased tendency for IL-10 has been shown in erosive and reticular OLP when compared to healthy controls. • This cytokine profile suggests a Th1/Th2 imbalance towards the Th2 response in OLP • Overexpression of IL-22, IL-23, IL-18 and IL-17 in OLP patients could suggest a role for these cytokines in the pathogenesis of OLP 28,45,46,50 CXCL10, CXCL11 and chemokine (C-C motif) ligand (CCL) 5.…”

“…29 Recently, it has been shown that both CD40 and CD86 are constitutively expressed at low levels in oral keratinocytes, specifically the H357 squamous cell carcinoma cell line and three strains of primary normal oral keratinocytes, and that expression was enhanced by IFN-γ stimulation. 30 IHC was used to further evaluate the involvement of CD40 in OLP with results showing strong intensity of CD40 staining in OLP tissues. 30 Overall, the results of this study strongly suggest that CD40 and CD86 may play an important pathophysiologic role in oral inflammatory diseases like OLP.…”

“…30 IHC was used to further evaluate the involvement of CD40 in OLP with results showing strong intensity of CD40 staining in OLP tissues. 30 Overall, the results of this study strongly suggest that CD40 and CD86 may play an important pathophysiologic role in oral inflammatory diseases like OLP. 30 Moreover, a recent study assessed the production of keratinocyte-derived CXCL9/10/11 under basal and inflammatory conditions as well as the role these chemokines may play in the pathogenesis of OLP.…”