Figure 2.

Endothelial activation mediated by histones induce Treg proliferation. (A) Comparison of Treg expansion after three days of coculture, with HMECs, pre-stimulated or not with histones, and with or without TAK 242 pre-incubation. Results are presented as the percentage of CD4⁺ CD25⁺ CD127^low FoxP3^high among CD4⁺ cells. Gating was performed using Fluorescence Minus One (FMO) control. Histone pre-treatment increased Treg expansion (Kruskal–Wallis test, ** p = 0.002), and this was strongly reduced by TLR4 inhibition (Kruskal-Wallis test, * p = 0.011, (n = 18–73)). (B) IL-6 was measured in co-culture supernatants. Histone pre-treatment increased IL-6 secretion in co-culture, and this was not reversed by TLR4 inhibition (Kruskal–Wallis test, **** p < 0.0001 (n = 12–23)).