Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk

Partnerzy

K. Biswas Subhra


Ostatnie publikacje
1.  Kalliara E., Kardynska M., Bagnall J., Spiller David G., Müller W., Ruckerl D., Śmieja J., Biswas Subhra K., Paszek P., Post-transcriptional regulatory feedback encodes JAK-STAT signal memory of interferon stimulation, Frontiers in Immunology, ISSN: 1664-3224, DOI: 10.3389/fimmu.2022.947213, Vol.13, pp.947213-1-19, 2022

Streszczenie:
Immune cells fine tune their responses to infection and inflammatory cues. Here, using live-cell confocal microscopy and mathematical modelling, we investigate interferon-induced JAK-STAT signalling in innate immune macrophages. We demonstrate that transient exposure to IFN-γ stimulation induces a long-term desensitisation of STAT1 signalling and gene expression responses, revealing a dose- and time-dependent regulatory feedback that controls JAK-STAT responses upon re-exposure to stimulus. We show that IFN-α/β1 elicit different level of desensitisation from IFN-γ, where cells refractory to IFN-α/β1 are sensitive to IFN-γ, but not vice versa. We experimentally demonstrate that the underlying feedback mechanism involves regulation of STAT1 phosphorylation but is independent of new mRNA synthesis and cognate receptor expression. A new feedback model of the protein tyrosine phosphatase activity recapitulates experimental data and demonstrates JAK-STAT network’s ability to decode relative changes of dose, timing, and type of temporal interferon stimulation. These findings reveal that STAT desensitisation renders cells with signalling memory of type I and II interferon stimulation, which in the future may improve administration of interferon therapy.

Słowa kluczowe:
JAK-STAT network, STAT1 kinetics, interferons, pathway desensitisation, mathematical modelling, signal memory, live-cell microscopy

Afiliacje autorów:
Kalliara E. - inna afiliacja
Kardynska M. - inna afiliacja
Bagnall J. - inna afiliacja
Spiller David G. - inna afiliacja
Müller W. - inna afiliacja
Ruckerl D. - inna afiliacja
Śmieja J. - Silesian University of Technology (PL)
Biswas Subhra K. - inna afiliacja
Paszek P. - IPPT PAN
140p.

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