TNF-α sculpts a maturation process in vivo by pruning tolerogenic dendritic cells.

It remains unclear how the pro-immunogenic maturation of conventional dendritic cells (cDCs) abrogates their tolerogenic functions. Here, we report that the loss of tolerogenic functions depends on the rapid death of BTLAhi cDC1s, which, in the steady state, are present in systemic peripheral lymphoid organs and promote tolerance that limits subsequent immune responses. A canonical inducer of maturation, lipopolysaccharide (LPS), initiates a burst of tumor necrosis factor alpha (TNF-α) production and the resultant acute death of BTLAhi cDC1s mediated by tumor necrosis factor receptor 1. The ablation of these individual tolerogenic cDCs is amplified by TNF-α produced by neighboring cells. This loss of tolerogenic cDCs is transient, accentuating the restoration of homeostatic conditions through biological turnover of cDCs in vivo. Therefore, our results reveal that the abrogation of tolerogenic functions during an acute immunogenic maturation depends on an ablation of the tolerogenic cDC population, resulting in a dynamic remodeling of the cDC functional landscape. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Courtney A Iberg, Jessica Bourque, Ian Fallahee, Sungho Son, Daniel Hawiger. TNF-α sculpts a maturation process in vivo by pruning tolerogenic dendritic cells. Cell reports. 2022 Apr 12;39(2):110657

Mesh Tags

Substances

PMID: 35417681

search → result