Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation

Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation

Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4<sup>+</sup>, CD4<sup>+</sup>CD25<sup>+</sup>, and CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>, which are cr...

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Main Authors:	Valentina Yu, Marina Balabekova, Assel Ten, Tolganay Zharkynbek, Sulev Koks, Milana Alimova, Raushan Koizhaiganova, Meruyert Mussilim, Aigul Malmakova, Tulegen Seilkhanov, Khaidar Tassibekov
Format:	Article
Language:	English
Published:	MDPI AG 2025-06-01
Series:	Molecules
Subjects:	complex of dimethyl[(4-benzhydrylpiperazin-1-yl)(2-fluorophenyl)methyl]phosphonate with β-Cyclodextrin ((<b><i>o</i>-Fph</b>)<b>PPhβCD</b>) Polyoxidonium (PO) acute pneumonia regulatory T cells immunomodulation
Online Access:	https://www.mdpi.com/1420-3049/30/13/2741
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Summary:	Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4<sup>+</sup>, CD4<sup>+</sup>CD25<sup>+</sup>, and CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin ((<b><i>o</i>-Fph</b>)<b>PPhβCD</b>), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> significantly restored CD4<sup>+</sup> and CD4<sup>+</sup>CD25<sup>+</sup> T-cell levels and induced a sustained reduction in regulatory CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> exerted a more prolonged response, which was particularly evident by day 14. Structural confirmation of the inclusion complex was achieved through IR and NMR spectroscopy. These findings highlight (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation.
ISSN:	1420-3049