Noisy NFkB oscillations stabilize and sensitize cytokine signaling in space

TL;DR

This paper investigates how noisy, lower-amplitude NF-kB oscillations enhance the stability and sensitivity of cytokine signaling in spatially distributed cells, revealing their potential evolutionary role in immune response robustness.

Contribution

It introduces a cellular automaton model showing that noisy secondary oscillations stabilize wave patterns and may prevent chronic inflammation, highlighting their functional significance.

Findings

Noisy secondary oscillations stabilize wave patterns.

Lower amplitude and noise may prevent chronic inflammation.

Oscillations increase robustness of inflammatory response.

Abstract

NF-kB is a major transcription factor mediating inflammatory response. In response to pro-inflammatory stimulus, it exhibits characteristic response -- a pulse followed by noisy oscillations in concentrations of considerably smaller amplitude. NF-kB is an important mediator of cellular communication, as it is both activated by and upregulates production of cytokines, signals used by white blood cells to find the source of inflammation. While the oscillatory dynamics of NF-$\kappa$B has been extensively investigated both experimentally and theoretically, the role of the noise and the lower secondary amplitude has not been addressed. We use a cellular automaton model to address these issues in the context of spatially distributed communicating cells. We find that noisy secondary oscillations stabilize concentric wave patterns, thus improving signal quality. Furthermore, both lower secondary amplitude as well as noise in the oscillation period might be working against chronic inflammation, the state of self-sustained and stimulus-independent excitations. Our findings suggest that the characteristic irregular secondary oscillations of lower amplitude are not accidental. On the contrary, they might have evolved to increase robustness of the inflammatory response and the system's ability to return to pre-stimulated state.