The Potential Immunomodulatory Roles of Semaphorin 4D in Human Periapical Lesions

Introduction: Semaphorin 4D (SEMA4D) is an important immunoregulator in the development of inflammatory diseases. Currently, the role of SEMA4D in human apical periodontitis remains unclear. This study aims to investigate the expression of SEMA4D and its potential immunomodulatory roles in apical periodontitis.

Methods: A total of 31 periapical tissues and 6 healthy gingival tissues were used in this experiment. Hematoxylin-eosin staining, immunohistochemical staining, and multiplex immunofluorescence staining were performed for histologic examination and immunochemical analysis. For data processing, the number of SEMA4D⁺, CD4⁺, CD8⁺, and CD20⁺ cells was analyzed by QuPath. In addition, the colocalization of SEMA4D with CD4, CD8, and CD20 was detected.

Results: Radicular cysts (RCs) (n = 18) and periapical granulomas (PGs) (n = 13) were identified by histologic evaluation. The number of SEMA4D⁺ cells in PGs was significantly greater than that in RCs (P < .05). T-cell and B-cell infiltration did not differ significantly between RCs and PGs. An increased number of CD20⁺ cells was observed in both types of apical periodontitis compared to CD8⁺ cells and CD4+ cells. Additionally, the presence of SEMA4D/CD4 and SEMA4D/CD20 double-positive cells was also markedly higher in PGs than in RCs.

Conclusion: The expression of SEMA4D and related immune cells showed different characteristics between RCs and PGs. The disparate expression patterns indicated the possible different pathologic states of the 2 types of periapical lesions. This study provides a new perspective on the description of the comprehensive microenvironment of periapical lesions.