Format

Send to

Choose Destination
J Cell Sci. 2019 Oct 10;133(5). pii: jcs234781. doi: 10.1242/jcs.234781.

Membrane trafficking as an active regulator of constitutively secreted cytokines.

Author information

1
Tumor Immunology Lab, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, 6500HB Nijmegen, The Netherlands.
2
Tumor Immunology Lab, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, 6500HB Nijmegen, The Netherlands g.van.den.bogaart@rug.nl.
3
Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747AG Groningen, The Netherlands.

Abstract

Immune-cell activation by inflammatory stimuli triggers the transcription and translation of large amounts of cytokines. The transport of newly synthesized cytokines to the plasma membrane by vesicular trafficking can be rate-limiting for the production of these cytokines, and immune cells upregulate their exocytic machinery concomitantly with increased cytokine expression in order to cope with the increasing demand for trafficking. Whereas it is logical that trafficking is rate-limiting for regulated secretion where an intracellular pool of molecules is waiting to be released, the reason for this is not obvious for constitutively secreted cytokines, such as interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α). These constitutively secreted cytokines are primarily regulated at the transcriptional and/or translational level but mounting evidence presented here shows that cells might also increase or decrease the rate of post-Golgi cytokine trafficking to modulate their production. Therefore, in this Hypothesis, we ask the question: why is there a need to limit the trafficking of constitutively secreted cytokines? We propose a model where cells monitor and adjust their production rate of cytokines by sensing the intracellular level of cytokines while they are in transit to the plasma membrane. This self-regulation of cytokine production could prevent an overshooting response of acute-phase cytokines, such as IL-6, IL-12 and TNF-α, upon acute infection.

KEYWORDS:

Cytokine secretion; Exocytosis; Interleukin 6; Membrane trafficking

PMID:
31601617
DOI:
10.1242/jcs.234781

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

Publication type

Publication type

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center