Innate Immune Activation Is a Strong Suppressor of CCL22 and Impedes Regulatory T Cell–Dendritic Cell Interaction
Year: 2025
Type: article
Abstract: The chemokine CCL22 is constitutively expressed at high levels in lymphoid organs, where it controls immunity by promoting contacts between dendritic cells (DC) and regulatory T cells (Treg). However, its regulation and impact in the context of pattern recognition receptor (PRR) stimulation and microbial infection are unknown. Here we show that CCL22 levels in lymphoid organs of mice were strongly suppressed upon stimulation with TLR agonists. In vitro, activation of Toll-like receptors (TLR), RIG-I like helicases (RLH) and stimulator of interferon genes (STING) resulted in a potent downregulation of CCL22. Mechanistically, the suppression of DC-derived CCL22 secretion was exerted by inflammatory cytokines such as IFN-α, IFN-γ and IL-10 released upon TLR activation by B and T cells. Decreased CCL22 synthesis correlated with reduced frequencies of cellular clustering between Treg and DC in co-cultures. CCL22 suppression was also observed upon microbial infection, since CCL22 levels were significantly reduced in lymphoid organs of mice upon injection of Salmonella typhimurium. As a clinical correlate, CCL22 serum concentrations were decreased in patients with sepsis compared to controls. Taken together, we demonstrate a strong and long-lasting suppression of CCL22 as a consequence of innate immune activation. In the context of microbial infection, transient reduction of CCL22 reduces Treg-DC interactions and may thereby represent a mechanism to weaken Treg function in order to enable an effective immune response and pathogen clearance.
Source: Immunology
DOI: 10.1111/imm.13926
Authors: Ignazio Piseddu, Jan Gärtig, Stephan Eiber, Stefan Moder, Raffael Thaler, Matthias Thaler, Juliane Gruen, Marlies Vornhülz, Kevin Bahner, Luana Messa, Benjamin Kühnemuth, Jennifer Müller, Konstantin Schnell, Antonia Beimert, Carolin Perleberg, Natascha Röhrle, Maximilian Martin Ludwig Knott, Linda Hammann, Vanessa Wittmann, Patrick Layritz, Moritz Rapp, Carole Bourquin, Julia Mayerle, Stefan Endres, David Anz
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,330
OpenAlex ID: W4408885097