Immunohistochemical Evidence Linking Interleukin-22 Tissue Expression Levels to FOXP3+ Cells and Neutrophil Densities in the Mycosis Fungoides Microenvironment.

Abstract

Emerging data indicate that the cellular microenvironment and interleukins (IL) play a crucial role in mycosis fungoides (MF).We aimed to explore the potential association between the composition of the cellular microenvironment and the expression of IL-22 and IL-17A in MF skin lesions. The study encompassed 16 cases of MF of different stages, for which sufficient skin tissue for immunohistochemistry and frozen tissue for reverse transcription-polymerase chain reaction, both taken from the same lesion, were available. Histological evaluation of eosinophils, neutrophils, CD20+, CD4+, CD8+, FOXP3+, CD56+, and CD1a+ cells was conducted. Additionally, mRNA expression levels of IL-22 and IL-17 mRNA were quantified using reverse transcription-quantitative polymerase chain reaction.SPSS version 28 (IBM Corp., Armonk, NY) was utilized for statistical analysis. Among the cases examined, three were in the patch stage, eight in the plaque stage, and five in the transformation to high-grade large cell lymphoma (t-LCL). B-lymphocytes, neutrophils, and eosinophilswere primarily observed in t-LCL cases. IL-22 levels displayed a significant association with IL-17A levels (Pearson'sr = 0.961, p < 0.001), FOXP3+ cells (Pearson'sr = 0.851, p < 0.001), and neutrophil density (Pearson'sr = 0.586, p = 0.014). No correlation was detected between IL-17A levels and the evaluated subtypes of microenvironmental cells. The microenvironment of MF lesions with t-LCL is noticeably different from early MFin terms of cellular composition. Histopathological identification of the cellular microenvironment may serve as an indicator of IL-22 tissue levels. These results implicate certain types of cells in IL-22 expression in the MF microenvironment and may contribute to advancing our knowledge on the pathogenesis and progression of the disease.