The Activation of NF-κB in Infiltrated Mononuclear Cells Negatively Correlates with Treg Cell Frequency in Oral Lichen Planus
Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucosal disease with persistent accumulation of T cells in the lamina propria. Nuclear factor-kappa B (NF-κB) is a major regulator of immune responses, and NF-κB-dependent cytokines and pro-inflammatory mediators can be detected in higher levels in the saliva and serum from patients with OLP. CD4+CD25+Foxp3+ regulatory T (Treg) cells play an important role in the prevention of autoimmune pathology by regulating the immune response. To explore the correlation between NF-κB p65 activation and accumulation of Treg cells in patients with OLP, 40 ethnic Chinese patients with OLP and 10 healthy volunteers were recruited. The nuclear expression of NF-κB p65 in infiltrated mononuclear cells and Treg cells in the OLP lesion and the normal oral mucosa (NOM) was analyzed by immunohistochemistry assay. Our results showed that both the nuclear expression of NF-κB p65 and the number of Foxp3+ Treg were higher in the OLP lesions. Furthermore, the frequency of Treg cells was negatively correlated with NF-κB nuclear expression in subepithelial lymphocytic infiltrate of the OLP lesion. This finding provides a new insight into the pathogenesis of OLP and may contribute to novel therapeutic strategies for the treatment of OLP by modulating the immune system.
KEY WORDSOLP Foxp3 NF-κB inflammation immunotherapy
We are particularly grateful to Dr. Eric Tu from the National Institute of Dental and Craniofacial Research (NIDCR/NIH, USA) for critical reading and suggestions for the manuscript. We thank the 111 Project of MOE & ISTCPC (2012DFA31370), China; and the National Natural Science Foundation of China (document no.: 81321002, 81472533 and 81400525)
Compliance with Ethical Standards
The authors declare that there is no potential conflict of interest. This study was approved by the Department of Oral Medicine, West China Hospital of Stomatology of Sichuan University, and the Committee for the Use of Human Subjects in Research in Sichuan University, with informed consent by all human participants involved in this study.
- 5.Zhou, G., K. Xia, G.F. Du, X.M. Chen, X.Y. Xu, R. Lu, and H.M. Zhou. 2009. Activation of nuclear factor-kappa B correlates with tumor necrosis factor-alpha in oral lichen planus: A clinicopathologic study in atrophic-erosive and reticular form. Journal of Oral Pathology & Medicine 38: 559–564.CrossRefGoogle Scholar
- 20.Rhodus, N.L., B. Cheng, S. Myers, W. Bowles, V. Ho, and F. Ondrey. 2005. A comparison of the pro-inflammatory, NF-kappaB-dependent cytokines: TNF-alpha, IL-1-alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus patients. Clinical Immunology 114: 278–283.PubMedCrossRefGoogle Scholar
- 21.Rhodus, N.L., B. Cheng, S. Myers, L. Miller, V. Ho, and F. Ondrey. 2005. The feasibility of monitoring NF-kappaB associated cytokines: TNF-alpha, IL-1alpha, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus. Molecular Carcinogenesis 44: 77–82.PubMedCrossRefGoogle Scholar
- 25.Tarbell, K.V., L. Petit, X. Zuo, P. Toy, X. Luo, A. Mqadmi, H. Yang, M. Suthanthiran, S. Mojsov, and R.M. Steinman. 2007. Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. The Journal of Experimental Medicine 204: 191–201.PubMedCentralPubMedCrossRefGoogle Scholar
- 26.Tang, Q., K.J. Henriksen, M. Bi, E.B. Finger, G. Szot, J. Ye, E.L. Masteller, H. McDevitt, M. Bonyhadi, and J.A. Bluestone. 2004. In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. The Journal of Experimental Medicine 199: 1455–1465.PubMedCentralPubMedCrossRefGoogle Scholar
- 27.Webster, K.E., S. Walters, R.E. Kohler, T. Mrkvan, O. Boyman, C.D. Surh, S.T. Grey, and J. Sprent. 2009. In vivo expansion of T reg cells with IL-2-mAb complexes: Induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. The Journal of Experimental Medicine 206: 751–760.PubMedCentralPubMedCrossRefGoogle Scholar
- 28.Kasagi S, Zhang P, Che L, Abbatiello B, Maruyama T, Nakatsukasa H, Zanvit P, Jin W, Konkel JE, Chen W. 2014. In vivo-generated antigen-specific regulatory T cells treat autoimmunity without compromising antibacterial immune response. Science Translational Medicine 6: 241ra278.Google Scholar
- 34.Nishimura, K.N.N., E. Satoh, Y. Harada, M. Nakayama, T. Tokizane, T. Fukui, Y. Ono, H. Inoue, M. Shin, Y. Tsujimoto, H. Takayama, K. Aozasa, and A. Okuyama. 2001. Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. Journal of the National Cancer Institute 93: 1739–1746.PubMedCrossRefGoogle Scholar