A model for the integration of conflicting exogenous and endogenous signals by dendritic cells.
Phys Biol
; 15(5): 056001, 2018 05 16.
Article
em En
| MEDLINE
| ID: mdl-29360100
ABSTRACT
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. Backed by experimental measurements we present a theoretical model 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Fator de Necrose Tumoral alfa
/
Interleucina-10
/
Modelos Imunológicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Phys Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article