Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4⁺, CD4⁺CD25⁺, and CD4⁺CD25⁺FoxP3⁺, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin ((o-Fph)PPhβCD), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that (o-Fph)PPhβCD significantly restored CD4⁺ and CD4⁺CD25⁺ T-cell levels and induced a sustained reduction in regulatory CD4⁺CD25⁺FoxP3⁺ cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, (o-Fph)PPhβCD 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 (o-Fph)PPhβCD as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation.

Background/Objectives: Acute pneumonia remains one of the leading causes of mortality worldwide. The pathogenesis of the disease is determined by the nature of the host immune response. The balance between effector and regulatory T cells (Treg) is critical, as it determines the severity of inflammation and the regenerative capacity of lung tissue. The development of new approaches to modulate the immune response using promising synthetic compounds opens up the possibility of targeted cytokine balance restoration of cytokine balance and Tregs functions This study investigated the effects of the newly synthesized complex of 1-(2-Ethoxypropyl)-4-(pent-1-yn-1-yl)piperidin-4-yl Propionate with β-Cyclodextrin (MXF-22), on the populations of CD4⁺, CD4⁺CD25⁺ and CD4⁺FoxP3⁺ T cells in an oleic acid-induced acute lung injury rat model. Methods: Quantitative analysis of CD4⁺, CD4⁺CD25⁺, and CD4⁺FoxP3⁺ T cell subsets and serum IL-4 and TGF-β levels were determined by flow cytometry and ELISA assays, respectively. Results: The study revealed a significant decrease in the number of CD4⁺ T cells and their regulatory subsets (CD4⁺CD25⁺, CD4⁺FoxP3⁺) during acute pneumonia. Oral administration of MXF-22 contributed to a pronounced recovery of these parameters, accompanied by increased levels of IL-4 and TGF-β, which indicated the activation of anti-inflammatory and reparative processes. Conclusions: MXF-22 showed a pronounced immunomodulatory effect contributing to the restoration of the function of CD4⁺ FoxP3⁺ T regs in acute pneumonia rat model.

Relevance: Psoriasis is a chronic inflammatory disease characterized by its polygenic nature and the leading role of immune mechanisms. It is based on skin and joint damage. Clinically, the disease is characterized by erythematous rashes covered with silver scales. Despite significant progress in elucidating the pathogenesis and the introduction of targeted biological drugs, it has not yet been possible to achieve sustainable, long-term disease control. In this regard, there is a pressing need to develop new therapeutic strategies targeting key links in the pathogenesis. The use of antisense oligonucleotides is considered a promising therapeutic approach. Objective: To analyze modern concepts of the immunopathogenesis of psoriasis and evaluate the therapeutic potential of antisense oligonucleotides. Materials and Methods: A literature search was conducted in the PubMed, Scopus, Web of Science, Google Scholar, ScienceDirect, and the Cochrane Library databases. Articles published from 2010 to September 2025 were selected for inclusion. Inclusion criteria comprised articles published in peer-reviewed journals focusing on the immune pathogenesis of psoriasis, the IL-23/IL-17 and IL-36 signaling axes, and the therapeutic potential of antisense oligonucleotides. Only publications with full-text availability and direct relevance to the research topic were considered for inclusion. Exclusion criteria included articles not directly relevant to the research topic, duplicate publications, conference abstracts, letters to the editor, and studies without full-text availability. Results: Analysis of recent articles in international scientific databases highlights the importance of the IL-23/IL-17 and IL-36 axes in the development of psoriasis. These signaling pathways support chronic inflammation and promote the pathological proliferation of keratinocytes. Moreover, the obtained data indicate that antisense oligonucleotides may represent a promising approach for pathogenetic therapy and can expand the possibilities for targeted treatment of psoriasis. Conclusions: Psoriasis is a chronic immune-inflammatory disease. In its pathogenesis, the IL-23/IL-17 and IL-36 axes play a key role in the regulation of keratinocyte proliferation, leading to sustained inflammatory mechanisms. Antisense oligonucleotides used in its treatment selectively act on key pathogenic links by suppressing the expression of genes responsible for disease initiation. Although the aforementioned method represents one of the promising approaches for targeted intervention at the molecular level in the disease, there is a need for further in-depth investigation of its efficacy and safety before clinical implementation.

Psoriasis is a chronic immune-mediated inflammatory disease associated with dysregulation of T-cell responses and cytokine signaling. The aim of this study was to synthesize and structurally characterize a piperidine α-hydroxyphosphonate (OPP) and to comparatively evaluate the effects of OPP and the vivo-phosphorodiamidate morpholino oligomer (vPMO) in a preclinical model of imiquimod-induced psoriasis. OPP was synthesized by hydrophosphorylation of 1-(3-isopropoxypropyl)piperidin-4-one with dimethyl phosphite; its structure was confirmed by IR, NMR spectroscopy, and elemental analysis. Psoriasis was induced in rats by topical application of imiquimod (IMQ). The animals were randomly allocated into six groups: control (C), experimental psoriasis (Ps), vehicle-treated (Ps/V), glucocorticosteroid-treated (Ps/GCS), piperidine α-hydroxyphosphonate-treated (Ps/OPP), and vivo-phosphorodiamidate morpholino oligomer-treated (Ps/vPMO) groups. Clinical manifestations were assessed on Days 3, 5, and 7 using a modified Psoriasis Area and Severity Index (PASI). During the 7-day observation period, body weight and the modified Psoriasis Area and Severity Index (PASI) score were assessed on Days 3, 5, and 7. Histopathological changes were evaluated using hematoxylin and eosin (H&E) staining. On day 7, CD3⁺CD45R⁻, CD4⁺CD8⁻, and CD4⁺CD25⁺ T-cell subpopulations were determined by flow cytometry, while serum concentrations of IL-6, TNF-α, IL-10, TGF-β1, IL-17A, and IL-22 were measured using an enzyme-linked immunosorbent assay (ELISA). IMQ administration resulted in the progressive development of psoriasiform skin lesions characterized by hyperkeratosis, acanthosis, inflammatory infiltration of the dermis, body weight loss, decreased numbers of CD3⁺CD45R⁻ and CD4⁺CD8⁻ cells, increased levels of IL-6, IL-17A, and IL-22, and reduced IL-10 levels. OPP treatment was associated with a reduction in the total PASI score and the severity of scaling, as well as decreased serum concentrations of IL-6, IL-17A, and IL-22 and an increased IL-10 concentration. In addition, OPP increased the number of CD4⁺CD8⁻ cells compared with the psoriasis group, whereas the number of CD4⁺CD25⁺ cells remained below the control level. In contrast, vPMO treatment exhibited a distinct response profile characterized by increased numbers of CD3⁺CD45R⁻ and CD4⁺CD8⁻ cells, decreased IL-17A and IL-22 levels, increased IL-10 levels, and a particularly pronounced increase in TGF-β1 while producing less pronounced changes in certain cutaneous manifestations. Overall, OPP was characterized by a more consistent pattern of clinical, histopathological, and immunological changes, whereas vPMO treatment predominantly resulted in more pronounced alterations in systemic immunological parameters. These findings indicate distinct patterns of biological effects of OPP and vPMO in the IMQ-induced psoriasiform skin lesion model and support further preclinical investigation of these compounds. However, the observed changes do not allow definitive conclusions to be drawn regarding the underlying molecular mechanisms or the involvement of specific cellular pathways and should be interpreted in light of the limited observation period, the restricted panel of cellular markers examined, the absence of certain experimental controls, and the lack of pharmacokinetic data.