Figure 5.

HMGB1 drives the accumulation and function of MDSCs. (A) Activation of T cells within lymph nodes requires that naive T cells express L-selectin so they can extravasate from the circulation and enter lymph nodes. MDSCs impair this process through their plasma membrane expression of ADAM17, an enzyme that cleaves L-selectin. L-selectin cleavage is exacerbated by HMGB1-activated MDSCs. (B) HMGB1 enhances MDSC production of IL-10. (C) HMGB1 increases PMN-MDSC expression of TLR4 and RAGE, and these MDSCs drive NETosis. MDSC-driven NETosis and MDSC migration are stimulated by complement C5a. (D) HMGB1 drives the differentiation of common myeloid progenitor cells (CMPs) toward MDSCs at the expense of dendritic cells (DCs) and plasmacytoid DCs (pDCs) resulting in a decrease in DCs and pDCs. (E) HMGB1 drives MDSC autophagy and survival.