A Mathematical Framework for Understanding Four-Dimensional Heterogeneous Differentiation of CD4+ T Cells

Bulletin of Mathematical Biology
Tian HongJohn J Tyson

Abstract

At least four distinct lineages of CD4+ T cells play diverse roles in the immune system. Both in vivo and in vitro, naïve CD4+ T cells often differentiate into a variety of cellular phenotypes. Previously, we developed a mathematical framework to study heterogeneous differentiation of two lineages governed by a mutual-inhibition motif. To understand heterogeneous differentiation of CD4+ T cells involving more than two lineages, we present here a mathematical framework for the analysis of multiple stable steady states in dynamical systems with multiple state variables interacting through multiple mutual-inhibition loops. A mathematical model for CD4+ T cells based on this framework can reproduce known properties of heterogeneous differentiation involving multiple lineages of this cell differentiation system, such as heterogeneous differentiation of TH1-TH2, TH1-TH17 and iTReg-TH17 under single or mixed types of differentiation stimuli. The model shows that high concentrations of differentiation stimuli favor the formation of phenotypes with co-expression of lineage-specific master regulators.

References

Oct 21, 1991·Journal of Theoretical Biology·E MjolsnessJ Reinitz
Jan 1, 1972·Biophysical Journal·H R Wilson, J D Cowan
Mar 1, 1996·The Journal of Experimental Medicine·E MurphyA O'Garra
Jun 25, 2002·Journal of Theoretical Biology·Olivier Cinquin, Jacques Demongeot
Jun 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Thomas HöferReinhart Heinrich
Feb 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Saritha KusamAlexander L Dent
Mar 4, 2003·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Jan 18, 2005·Journal of Theoretical Biology·Olivier Cinquin, Jacques Demongeot
Jan 22, 2005·Science·Eun Sook HwangLaurie H Glimcher
Mar 6, 2007·The Journal of Comparative Neurology·Melanie L BellSteven G Britt
Apr 7, 2007·Developmental Biology·Sui HuangTariq Enver
Sep 4, 2008·International Immunology·Henk-Jan van den Ham, Rob J de Boer
Dec 2, 2008·PLoS Computational Biology·Raúl Guantes, Juan F Poyatos
Jan 9, 2010·Annual Review of Physical Chemistry·John J Tyson, Béla Novák
Mar 3, 2010·Annual Review of Immunology·Jinfang ZhuWilliam E Paul
Jul 21, 2010·Nature Immunology·Kenneth M Murphy, Brigitta Stockinger
Sep 9, 2010·PLoS Computational Biology·Aurélien NaldiDenis Thieffry
Oct 22, 2010·Nature·Kamran GhoreschiJohn J O'Shea
Feb 15, 2011·Annual Review of Immunology·Shane Crotty
Apr 5, 2012·Clinical & Developmental Immunology·Rishi Vishal LuckheeramBing Xia
Aug 23, 2012·PLoS Computational Biology·Robert Clewley
Jan 31, 2013·Bulletin of Mathematical Biology·Luis Mendoza
Mar 16, 2013·Science·Carmen GerlachTon N M Schumacher
Aug 13, 2013·PLoS Biology·Miaoqing FangAlexander van Oudenaarden

❮ Previous
Next ❯

Citations

Mar 27, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Tilmann GlimmStuart A Newman
Sep 1, 2016·Discrete and Continuous Dynamical Systems. Series B·Catherine Ha TaTian Hong
Dec 7, 2018·Journal of Theoretical Biology·John J TysonPavel Kraikivski
Dec 19, 2020·Computational and Structural Biotechnology Journal·Ziyi LiuTian Hong

❮ Previous
Next ❯

Related Concepts

Related Feeds