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. 2023 Jan 24;14:1092801. doi: 10.3389/fimmu.2023.1092801

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Copyright © 2023 Reuter, Raspe, Uebner, Contoyannis, Pastille, Westendorf, Caso, Cover, Müller and Taube

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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VacA modulates expression of stimulatory and inhibitory co-receptors and cytokines in murine and human dendritic cells (DC) and induces humanregulatory T cells (Tregs). (A) Treatment scheme: murine bone marrow DC (BMDC)/human DC: after 7 days of differentiation DC were treated +/-allergen (all), then DC activation (act.) was performed and treatment with VacA was given. Cultivation of human DC with autologous T cells wasperformed from day 10–14. (B) Change in expression of the indicated surface marker after treatment with VacA versus naïve, activated, or activated andallergen-supplemented murine and human DC. (C) Supernatant concentrations of interleukin (IL)-10 in naïve, activated, and activated and allergensupplementedmurine and human DC cultures with or without VacA. (D) Change in expression of the indicated surface marker with inhibitory capacityversus VacA treatment on the surface of naïve, activated, or activated and allergen-supplemented human DC (murine, n=14; human, n=10). AutologousT cells were cultured with the differentially activated and VacA-treated DC and the proportion of regulatory T cells was then examined. (E) Dot plots:regulatory T cells were identified by gating CD25+/CD127- cells within the population of CD4+/CD3+ T helper cells. Dot plots show representativeexamples for CD25/CD127 staining of naïve, activated, and activated and allergen-supplemented human DC/T cell cultures with or without VacAtreatment. Gate and proportion of Tregs is highlighted. (F) Percentage of Tregs within the CD4+ T cell population. VacA treatment significantly increasedTregs in all analyzed culture conditions (n=10). Wilcoxon signed rank test: *p<0.05, **p<0.01, ***p<0.001.