JCI - In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF-α

In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF-α

Michael K. Connolly, Andrea S. Bedrosian, Jon Mallen-St. Clair, Aaron P. Mitchell, Junaid Ibrahim, Andrea Stroud, H. Leon Pachter, Dafna Bar-Sagi, Alan B. Frey, George Miller

Published in Volume 119, Issue 11

J Clin Invest. 2009; 119(11):3213–3225 doi:10.1172/JCI37581

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Figure 2

DCs control the inflammatory milieu in liver fibrosis.

(A) Freshly isolated liver DCs were cultured for 24 hours at a concentration of 1 × 10⁶. FLDCs produced more than 2-fold elevation in TNF-α compared with controls (P < 0.05). TNF-α production was further enhanced as a result of TLR9 ligation, but not TLR3, TLR4, or TLR5 ligation. (B) Similarly, FLDCs also produced elevated levels of IL-6 (P < 0.05). (C–E) NPCs were harvested from the livers of normal and fibrotic mice and cultured for 24 hours at a concentration of 1 × 10⁶. Depletion of DCs from fibrotic NPC concentrates by FACS abrogated their elevated cytokine and chemokine production (P < 0.05 for each inflammatory mediator). (F) Freshly isolated NPCs from unmanipulated CD11c-DTR mice, fibrotic CD11c-DTR mice, or fibrotic CD11c-DTR mice that were depleted of DCs for 48 hours immediately prior to sacrifice were cultured as above. Cell culture supernatant was then assayed for inflammatory mediators. DC depletion in vivo in fibrotic mice markedly decreased NPC cytokine and chemokine production (P < 0.05 for each inflammatory mediator).