Relevance: At the present stage, it is known that Langerhans cells (CL) are of both myeloid and lymphoid origin, but the conditions for directed differentiation of progenitor cells have not been deciphered [1, 2]. There are attempts to create vaccines based on CL, however, the reasons and cellular interactions during the transmission of viral antigens under conditions of infection are unknown. A poorly studied structure under HPVI conditions is the oral mucosa, despite the fact that the human papillomavirus is included in the list of viruses that cause malignancy [3, 4, 5]. In this regard, the study of the role of Langerhans cells in the stabilization of cellular ensembles of the oral mucosa in the case of human papillomavirus contamination is of particular relevance.
Purpose of the study: To study the role of Langerhans cells in the overgrowth of the oral mucosa in human papillomavirus infection.
Material and methods: In the period from 2011 to 2018, we studied biopsies of the oral mucosa of 27 patients (18 men and 9 women) aged 31 to 67 years with confirmation of HPVI in the papillomas of the oral mucosa by PCR. The material was obtained in accordance with the instructions for the collection, transportation and storage of biological material in medical institutions. The control group consisted of 4 patients who died as a result of injuries incompatible with life, presumably without somatic pathology at the age from 24 to 76 years. The preparations are stained by the classical method with hematoxylin and eosin. Langerhans cells were detected by immunohistochemical method followed by analysis on a microscope Olympus-BKh-52.
Research results and their discussion: We found that when examining the material of papillomas with the etiology of HPVI, there is a decrease to complete disappearance of Langerhans cells in the epithelial layers with a proportionally increasing number of them in the connective tissue lamina adjacent to the epithelium.
We noted that the migration of CL from the epithelial layer is accompanied by an increase in the number of phenotypes of cells expressing CD4 and CD8 in the epithelium, as well as an increase in the number of cells labeled with Ki67, both in the epithelium and in the connective tissue (fig. 1, 2).
Figure: 1. The mucous membrane of the mouth of a 67-year-old patient with HPVI. Microphoto. Magnification x200.
A) staining with hematoxylin and eosin. B) Immunohistochemistry to identify the localization of Langerhans cells. Langerhans cells with localization in the epithelial cell layer are identified.
Figure: 2. The mucous membrane of the mouth of a 59-year-old patient with HPVI. Microphoto. Magnification x200.
A, B) Immunohistochemistry to identify the localization of Langerhans cells.
Langerhans cells with localization in the own connective tissue lamina of the oral mucosa are identified.
This indicates the role of CL in the induction of the immune response and the effect on the proliferative activity of mucosal structures. Although it was initially believed that Langerhans cells are located exclusively in the epidermis, current data indicate a wide range of CL localization in body tissues and complement the data of other authors on LC effects, such as transmission of viral antigens during herpes simplex infection, recruitment of eosinophils in HPVI and stimulation of the response Th17 for fungal infections. These CL responses are protective and provide additional evidence that T lymphocyte mechanisms are important in the host response to HPV-induced lesions. LC can perform a protective or suppressive function in the pathology of the oral mucosa, while the vector of function is determined by cell ensembles interacting with CL. These data provide additional evidence that the mechanisms of CL in the oral mucosa are important in the response of COP tissues to HPV-induced lesions.
In most of the studied samples, papillomavirus lesions in OSA were characterized by a decrease in the number of CD1a-positive phenotypes of cells with altered morphology. This, according to the authors, was accompanied by a decrease or loss of beta 2-microglobulin by epithelial cells.
These data are of particular importance for understanding the mechanisms of immunization using human papillomavirus (HPV) virus-like particles (VLPs), which induce a sustained and effective immune response. Evidence that HPV is hidden from immune surveillance with subsequent carriage in patients after HPV infection. CLs have the ability to induce an effective immune response to vaccination, but can also induce immune modulation during infection. The interaction of HPV-L1 VLPs with mucosal DC determines the immune response. However, little is known about the receptors on mucosal DC subpopulations involved in HPV-L1 VLP binding. 5. De Witte L., Zoughlami Y., Aengeneyndt B., et al (1993) confirmed the important role of syndecan-3 as an HPV receptor on DC, which is important not only in vaccine development, but also for understanding the pathogenetic mechanisms of HPV [6, 7, 8]. Lechien J.R., Seminerio I., Descamps G., et al. [7, 8].
It is known that long-term HPVI as a result of infection with the oncogenic human papillomavirus (HPV) can lead to cancer of the patients' mucous membranes. This dictates a pathogenetically adequate strategy acting in the conditions of the latent period of viral contamination. Taking into account the fact of spontaneous recovery or asymptomatic HPV carriage, it is necessary to investigate Langerhans cells as undeniable prognostic indicators of HPVI. Under these conditions, CL induce an immune response at the junction of innate and adaptive immunity, which plays an important role in the potential neutralization of HPV [9, 10, 11].
Conclusion. CD8, CD4, T-cells respond to HPV contamination, and their concentration in the oral mucosa is associated with the influence on the processes of regeneration of the COP structures. These cell phenotypes have predictive value. In infections caused by the human papillomavirus (HPV), Langerhans cells (LC) affect the pathogenesis of COP damage by viral infection and can be used as targets for inducing an immune response with the recruitment of immunocyte / macrophage assemblies for COP regeneration.
The study was financially supported by the International Medical Research and Education Center (Vladivostok, Russia).
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