Dendritic Cell Subsets And Their TOLL-Like Receptors In Oral Lichen Planus

Purpose:Oral lichen planus(OLP)is the most popular inflammation of oral mucosal,which is induced by T lymphocytes.Suffering a long treatment and a high recurrence,OLP patients commonly complain for the poor life quality.The main obstacle for the development of therapy in OLP,is that the pathogenic antigen is still keeping unknown.Dendritic cells(DCs)are the most powerful antigen presenting cells(APCs)in human,Toll-like receptors of DC perform as the chief molecules for recognizing the antigens and induce the T cells adaptive immunity.The research on DC-TLRs in OLP could be helpful to uncover the source and types of pathogen behind.Methods:Following the inclusion and exclusion criteria,the cases of OLP and healthy control(HC)were collected and their clinical background were recorded.(1)Four DC subsets were detected in peripheral blood mono-nuclear cells(PBMC)and in situ by FCM and IHC.They were CD11c~+mDC1,CD141~+mDC2,CD123~+pDC and CD207~+LC.Their frequencies in total PBMC were caculated between the OLP group and the HC group.And IHC tests observed their location in situ.(2)DC relative chemokines,chemokine receptors and cytokines'mRNAs were detected by qRT-PCR method in OLP lesions and HC tissues,for evaluating the DC subsets chemotaxis and function in-situ.(3)The TLRs mRNA in OLP and HC were tested by qRT-PCR,and the IHC tests were further performed for observing the highly expressed TLRs in-situ,so that the preponderant TLRs could be found.The highly expressed TLRs'signaling transduction pathways were tested by qRT-PCR and IHC tests,for verifying their activation in OLP lesions.Finally,based on the findings,the source and type of auto-antigen in OLP were summarized and speculated.Results:(1)No statistical difference was found for each DC subset in PBMC(p>0.05).In tissues,mDC1 and pDC subsets were statistically increased in OLP group comparing with HC group,while the others showed no difference.IHC staining verified the increasing infiltration of mDC1 and pDC subsets in OLP,and their infitration sites were closely accompanied by T cells locating at the epithelium-stroma interface.LC mainly infiltrated in epithelium and showed no statistical difference between OLP and HC.IHC staining showed a very poor indication for mDC2 subset so that it could not be evaluated.(2)Chemokines(CCL2/21 and CXCL9),chemokine receptors(CCR1/2/5/6/7 and CXCR3/4)and cytokine(IFN-?)were significantly up-regulated in OLP by qRT-PCR test,while IFN-?mRNA showed a slight increase with no statistical difference.(3)TLR1/2/4/7/8/9/10 were statistically up-regulated in OLP lesion,especially the TLR7/8/9(p<0.001).The qRT-PCR and IHC tests verified that TLR7/8/9 related MyD88-IRF7-IFN-?signaling pathway were activated in OLP.Conclusions:(1)No difference of each DC subset was found in PBMC of OLP patients and HC donors.MDC1 and pDC subsets was the main APC in OLP lesions.(2)The mDC1 and pDC related chemokines and their receptors were significantly up-regulated in OLP lesions,which was the molecular background for these two subsets'chemotaxis in situ.(3)The up-regulation of TLR7/8/9 and the activation of their downstream IRF7-IFN-?signaling pathway played as the key roles of the innate immunity in OLP.Summarized,it could be speculated that self-RNA/DNA or infected virus RNA/DNA from the epithelial cells might be the pathogenic antigens in OLP.