RT Journal Article
SR Electronic
T1 A model for the integration of conflicting exogenous and endogenous signals by dendritic cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 065706
DO 10.1101/065706
A1 Quentin Marcou
A1 Irit Carmi-Levy
A1 Coline Trichot
A1 Vassili Soumelis
A1 Thierry Mora
A1 Aleksandra M. Walczak
YR 2016
UL http://biorxiv.org/content/early/2016/07/25/065706.abstract
AB Cells of the immune system are confronted with opposing pro-and anti-inflammatory signals. Dendritic cells (DC) integrate these cues to make informed decisions whether to initiate an immune response. Confronted with exogenous microbial stimuli, DC endogenously produce both anti-(IL-10) and pro-inflammatory (TNFα) cues whose joint integration controls the cell's final decision. We combine experimental measurements with theoretical modeling to quantitatively describe the integration mode of these opposing signals. We propose a two step integration model that modulates the effect of the two types of signals: an initial bottleneck integrates both signals (IL-10 and TNFα), the output of which is later modulated by the anti-inflammatory signal. We show that the anti-inflammatory IL-10 signaling is long ranged, as opposed to the short-ranged pro-inflammatory TNFα signaling. The model suggests that the population averaging and modulation of the pro-inflammatory response by the anti-inflammatory signal is a safety guard against excessive immune responses.