Nguyen, Dao X; Baldwin, Helen M; Ezeonyeji, Amara N; Rohan Butt, Mohammed; Ehrenstein, Michael R; (2021) Regulatory T cells enhance Th17 migration in psoriatic arthritis which is reversed by anti-TNF. iScience , 24 (9) , Article 102973. 10.1016/j.isci.2021.102973.

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Abstract

Regulatory T cells (Treg) prevent the migration of effector T cells toward sites of inflammation, thereby limiting disease progression. We investigated this aspect of Treg function using psoriatic arthritis (PsA) as an exemplar of chronic inflammation. Patients with PsA had an increased Th17:Treg ratio which was reversed by anti-tumor necrosis factor (TNF) therapy. Utilizing an in vitro migration assay, Treg from patients with PsA treated with conventional therapy paradoxically boosted CCR6⁺ effector T-cell (a surrogate for Th17) migration toward CCL20. In contrast, Treg from patients with PsA treated with anti-TNF suppressed CCL20-driven effector T-cell migration. The boosting effect of TNF blockade upon Treg suppression of migration was accompanied by increased effector T-cell CCL20 production and enhanced interaction between Treg and effector T cells. This study provides mechanistic insight into Treg modulation of effector T-cell migration in patients with chronic inflammation and how this can be targeted by therapy.

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