Journal Article

Induction of high numbers of T reg cells post treatment with anti-IL-2/IL-2 complex associates with alleviation of experimental psoriasis-like skin inflammation

Abdel-Latif, Amany Mohammed, Salem, Mohamed Labib, Khalil, Sohaila M, Salman, Samar, El Attar, Yasmina Ahmed

2025

Overview

Psoriasis is a prevalent autoimmune skin disorder; however, the mechanism of its pathogenesis remains fully understood. The imbalance of regulatory T (T ) cells and effector T cells represents one potential mechanism, where a low dose of IL-2 is important. Given that IL-2/IL-12 complex is considered as an immune modulator for antigen-activated lymphocyte proliferation, this study aimed to compare the immunophenotypic, clinical, and histological effects of anti-IL-2/IL-2 complex to a low dose of free IL-2 on experimental psoriasis-like skin inflammation induced by imiquimod. Thirty-five Balb/c male mice were left without treatment, or were received topical application of imiquimod (IMQ, 3.125 mg/mouse) to induce psoriasis-like skin inflammation, and then the mice were treated with intraperitoneal (i.p.) injection of 100 µL containing anti-IL-2/IL-2 complex (2.5 µg /0.5 µg/mouse), or topical steroids (62.50 mg/mouse), or low dose of free IL-2 (i.p.; 0.5 µg/mouse). The expression levels of CD4, CD25, and Foxp3 in the leukocytes were assessed by multiparametric flow cytometry. The effects of different treatments on the histology and pathology of the induced psoriasis were also assessed. IMQ-induced hyperkeratosis, parakeratosis and mild papillomatosis with the retained nuclei in the keratin layer, whereas acanthosis with exocytosis was prominent in the epidermal layer. Lymphocyte infiltration was profusely all over the dermis. Additionally, there were some degrees of Munro micro abscesses were observed in the keratin layer with a collection of neutrophils in the group treated with standard betamethasone cream which showed mild improvement clinically, histopathological with no significant difference between this group and the naïve and positive control groups. After 7 days from the onset of treatment, we found that treatment of mice with anti-IL-2/IL-2 complex decreased the thickness of the epiderms as compared to their groups. Furthermore, the relative number of CD4 Foxp3 CD25  cells showed increases in psoriasis mice treated with anti-IL-2/IL-2 complex as compared to other groups. Anti IL-2/IL-2 complex therapy effectively ameliorated the clinical manifestations of psoriasis, with no apparent side effects, providing a new strategy for treating psoriasis.

• Subject: Animals / Disease Models, Animal / Imiquimod / Inflammation - immunology / Interleukin-2 - antagonists & inhibitors / Interleukin-2 - immunology / Male / Mice / Mice, Inbred BALB C / Psoriasis - chemically induced / Psoriasis - drug therapy / Psoriasis - immunology / Psoriasis - pathology / Psoriasis - therapy / Skin - drug effects / Skin - immunology / Skin - pathology / T-Lymphocytes, Regulatory - drug effects / T-Lymphocytes, Regulatory - immunology