Effect of IL-7 receptor blockade on IL-4 and IFN-γ production by memory CD4+ cells in patients with psoriasis vulgaris

Kolerova A.V.; Blinova E.A.; Kozlov V.A.; Sergeeva I.G.

doi:https://doi.org/10.17116/klinderma202221021194

Kolerova A.V.

Novosibirsk State University

ORCID: 0000-0003-0688-6175

Blinova E.A.

Novosibirsk National Research State University

Kozlov V.A.

Vishnevsky National Medical Research Center of Surgery

SPIN RSCI: 5917-6510
Scopus AuthorID: 57215343590
ORCID: 0000-0002-4926-116X

Sergeeva I.G.

Novosibirsk State University

Scopus AuthorID: 57044473200
ORCID: 0000-0003-1748-8957

Effect of IL-7 receptor blockade on IL-4 and IFN-γ production by memory CD4+ cells in patients with psoriasis vulgaris

Authors:

Kolerova A.V., Blinova E.A., Kozlov V.A., Sergeeva I.G.

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Journal: Russian Journal of Clinical Dermatology and Venereology. 2022;21(2): 194‑200

DOI: 10.17116/klinderma202221021194

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To cite this article:

Kolerova AV, Blinova EA, Kozlov VA, Sergeeva IG. Effect of IL-7 receptor blockade on IL-4 and IFN-γ production by memory CD4+ cells in patients with psoriasis vulgaris. Russian Journal of Clinical Dermatology and Venereology. 2022;21(2):194‑200. (In Russ.)
https://doi.org/10.17116/klinderma202221021194

Подписка 2026 Клиническая дерматология и венерология (Russian Journal of Clinical Dermatology and Venereology)

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BACKGROUND

Psoriasis is an autoimmune disease caused by dysfunction of Th1/Th17 T-lymphocytes. Recurrent rashes in psoriasis often occur in the same localizations due to the activity of resident memory T cells (Trm), which share a common origin with central memory T cells, the number of which correlates with PASI. IL-7 is the main cytokine that ensures the maintenance of memory CD4⁺ cell population. The features of the regulation of this cell population in psoriasis remain poorly understood.

OBJECTIVE

To study the effect of IL-7 receptor blockade (IL-7Rα) in vitro on IL-4 and IFN-γ production by CD4⁺-central (Tcm) and CD4⁺-effector (Tem) memory cells in patients with psoriasis.

MATERIAL AND METHODS

The study included 12 patients with psoriasis and 8 healthy donors (control group). Peripheral blood mononuclear cells were separated into adherent and nonadherent fractions. Nonadherent cells were used for magnetic sorting into CD4⁺-Tem and CD4⁺-Tcm. A portion of adherent fraction cells were treated with lipopolysaccharide (LPS), others were left untreated and cultured for 18-20 h. On day 2, sorted Tem and Tcm were added to it. Cytokine production activators were added on day 3. On day 4, cells were fixed, permeabilized, labeled with antibodies to CD4, CD45RO, CCR7, IL-4 and IFN-γ and flow cytometry was performed.

RESULTS

IL7Rα blockade inhibited the proliferation of Tcm and Tem memory cells in both healthy donors and psoriasis patients. In the control group, IL-7Rα blockade shifted the cytokine balance towards Th2, while in the group of psoriasis patients, the Th1/Th2 index remained unchanged, which may be explained by other regulatory mechanisms. The blockade decreased the number of Tem cells producing both IL-4 and IFN-γ in the presence of LPS but did not affect the number of Tem cells producing IL-4 (an inverse correlation was found between the number of these cells and PASI).

CONCLUSION

It can be assumed that the IL-7Rα blockade of CD4⁺ memory cells will increase the remission duration in psoriasis patients by inhibiting cell proliferation, decreasing the number of IL-4 and IFN-γ producers, and not affecting the Th2-pathway.

Keywords:

psoriasis

memory cells

IL-7

IL-7 receptor

immunological memory

Authors:

Kolerova A.V.

Novosibirsk State University

ORCID: 0000-0003-0688-6175

Blinova E.A.

Novosibirsk National Research State University

Kozlov V.A.

Vishnevsky National Medical Research Center of Surgery

SPIN RSCI: 5917-6510
Scopus AuthorID: 57215343590
ORCID: 0000-0002-4926-116X

Sergeeva I.G.

Novosibirsk State University

Scopus AuthorID: 57044473200
ORCID: 0000-0003-1748-8957

Received:

18.06.2021

Accepted:

22.03.2022

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