Abstract
(1) Background: Despite cleft lips and palates belonging to the most common orofacial congenital anomalies, their morphopathogenesis is not yet fully understood. The study aimed to determine the distribution and relation of cytokines interferon-γ (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-7, IL-12, and IL-13 in the cleft affected mucosa of the lip. (2) Materials and Methods: Twenty cleft lip (CL) mucosal samples and seven control tissues of oral cavity mucosa were included in the study. Specimen were obtained during reconstruction surgeries and processed by hematoxylin and eosin staining and immunohistochemistry for IFN-γ, TNF-α, IL-2, IL-7, IL-12, and IL-13. (3) Results: The distribution of cytokines was higher overall in the cleft affected epithelium compared to the connective tissue, with TNF-a, IL-2, and IL-12 displaying the highest number of immunopositive cells. With the exception of IL-2, CL specimen showed higher immunoreactivity. IFN-γ displayed only minor immunoreactivity, with no expression in the control epithelium. Correlation analysis was strongest between CL epithelial IL-13 and IFN-γ (z = 0.71, p < 0.0001). (4) Conclusions: The CLP affected epithelium displays high degrees of plasticity in expressing different cytokines, pointing towards the stimulation of a local adaptive immune response based on consistent inflammatory processes.
Highlights
We speculate that the increased levels of IFN-γ in line with TNF-α are successors of a sustained activation of M1 macrophages, which by themselves induce the prototypic T cell mediated chronic inflammatory response that we observed in the cleft tissue samples
We suggest that, considering the elevation of both cytokines IL-12 and IFN-γ, and given their association, that a profound interaction between T-cell and antigen presenting cells together with a raised activation of innate immune cells produces a persistent chronic inflammation in the cleft oral mucosa
The increase of IL-7, IFN-γ, and IL-12 in the cleft lips and palates (CLP) epithelium suggests the stimulation of local adaptive immune responses based on consistent inflammatory processes
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Orofacial clefts encompass a large group of congenital deformations with structural defects in the oral cavity and the adjacent facial framework. Within this group, the most common anomalies are cleft lips and palates (CLP), either occurring in isolation, in combined form, or as a part of an array of malformations [1]. The prevalence of CLP differs based on ethnicity, race, geographic location, and socioeconomic status [2], with 1.55 cases per 1000 live births in Europe [3]
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