Distinct patterns and kinetics of chemokine production regulate dendritic cell function

TLDR

Dendritic cells produce and respond to chemokines. The study aims to determine how chemokine production kinetics affect dendritic cell function during maturation. The authors examined chemokine production and responsiveness kinetics in dendritic cells during maturation. Chemokine production in dendritic cells shows distinct temporal patterns: inflammatory chemokines (MIP‑1α, MIP‑1β, IL‑8) peak rapidly and transiently, while constitutive chemokines (RANTES, MCP‑1, TARC, MDC, PARC, ELC) are sustained or up‑regulated during maturation, and receptor dynamics reveal CCR1/CCR5 down‑regulation, CCR7 up‑regulation and resistance to ligand‑induced down‑regulation, enabling dendritic cells to self‑regulate migration and recruit other immune cells.

Abstract

Dendritic cells (DC) have been showed to both produce and respond to chemokines. To understand how this may impact on DC function, we analyzed the kinetics of chemokine production and responsiveness during DC maturation. After stimulation with LPS, TNF-α or CD40 ligand, the inflammatory chemokines MIP-1α, MIP-1β and IL-8 were produced rapidly and at high levels, but only for a few hours, while RANTES and MCP-1 were produced in a sustained fashion. The constitutive chemokines TARC, MDC and PARC were expressed in immature DC and were up-regulated following maturation, while ELC was produced only at late time points. Activated macrophages produced a similar spectrum of chemokines, but did not produce TARC and ELC. In maturing DC chemokine production had different impact on chemokine receptor function. While CCR1 and CCR5 were down-regulated by endogenous or exogenous chemokines, CCR7 levels gradually increased in maturing DC and showed a striking resistance to ligand-induced down-regulation, explaining how DC can sustain the response to SLC and ELC throughout the maturation process. The time-ordered production of inflammatory and constitutive chemokines provides DC with the capacity to self-regulate their migratory behavior as well as to recruit other cells for the afferent and efferent limb of the immune response.