Biologics targeting IL-17 sharply reduce circulating T follicular helper and T peripheral helper cell sub-populations in psoriasis

Sotirios G Tsiogkas; Athanasios Mavropoulos; Efthimios Dardiotis; Efterpi Zafiriou; Dimitrios P Bogdanos

doi:10.3389/fimmu.2024.1325356

Biologics targeting IL-17 sharply reduce circulating T follicular helper and T peripheral helper cell sub-populations in psoriasis

Front Immunol. 2024 May 21:15:1325356. doi: 10.3389/fimmu.2024.1325356. eCollection 2024.

Authors

Sotirios G Tsiogkas¹, Athanasios Mavropoulos¹, Efthimios Dardiotis², Efterpi Zafiriou^#³, Dimitrios P Bogdanos^#¹

Affiliations

¹ Department of Rheumatology and Clinical Immunology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
² Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
³ Department of Dermatology, Faculty of Medicine, University of Thessaly, Larissa, Greece.

^# Contributed equally.

Abstract

Introduction: Circulating T follicular helper (cTfh) cells and circulating T peripheral helper (cTph) cells (which share common characteristics with the cTfh population) are implicated in the pathogenesis of immune-mediated and autoimmune diseases such as psoriasis (Ps). Their close interplay with the interleukin 17 (IL-17) axis and the ex vivo effect of IL-17-targeting biologic agents used to treat Ps on them are elusive. This study aimed to investigate the effect of biologics targeting IL-17 on cTfh and cTph cell subpopulations isolated from the blood of patients with Ps.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with Ps at treatment initiation and three months later. Samples were also collected from controls. Cells were stained using monoclonal antibodies. Flow cytometry assessed the fraction of cTfh (CD3⁺CD4⁺CXCR5⁺) and cTph (CD3₊CD4₊CXCR5_-PD-1_hi) cells..

Results: Flow cytometric analysis showed increased fractions of activated cTfh subsets including ICOS⁺ and ICOS⁺PD-1⁺ expressing cells, in patients compared to controls. Biologic blocking of IL-17A diminished the cTfh population. Furthermore, ICOS⁺ and ICOS⁺PD-1⁺ sub-populations were also inhibited. Finally, the cTph cell fraction significantly decreased after three months of successful treatment with biologics.

Conclusion: Early anti-IL-17-mediated clinical remission in Ps is associated with decreased cTfh and cTph cell subpopulations.

Keywords: PBMCs; anti-IL-17; brodalumab; cTfh; cTph; psoriasis; psoriatic disease; secukinumab.

MeSH terms

Adult
Biological Products* / pharmacology
Biological Products* / therapeutic use
Female
Humans
Interleukin-17* / antagonists & inhibitors
Interleukin-17* / metabolism
Male
Middle Aged
Psoriasis* / drug therapy
Psoriasis* / immunology
T Follicular Helper Cells / immunology
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
T-Lymphocytes, Helper-Inducer / drug effects
T-Lymphocytes, Helper-Inducer / immunology
T-Lymphocytes, Helper-Inducer / metabolism

Substances

Interleukin-17
Biological Products
IL17A protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The current research was supported in part by grants #5847 and #6606, University of Thessaly Research Committee (grant holder: DB).