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Plos Biology : Stochastic Cytokine Expression Induces Mixed T Helper Cell States, Volume 11

By Bhandoola, Avinash

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Book Id: WPLBN0003922712
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Biology : Stochastic Cytokine Expression Induces Mixed T Helper Cell States, Volume 11  
Author: Bhandoola, Avinash
Volume: Volume 11
Language: English
Subject: Journals, Science, Biology
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Biology
Historic
Publication Date:
Publisher: Plos

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Bhandoola, A. (n.d.). Plos Biology : Stochastic Cytokine Expression Induces Mixed T Helper Cell States, Volume 11. Retrieved from http://netlibrary.net/


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Description : During eukaryotic development, the induction of a lineage-specific transcription factor typically drives differentiation of multipotent progenitor cells, while repressing that of alternative lineages. This process is often mediated by some extracellular signaling molecules, such as cytokines that can bind to cell surface receptors, leading to activation and/or repression of transcription factors. We explored the early differentiation of naive CD4 T helper (Th) cells into Th1 versus Th2 states by counting single transcripts and quantifying immunofluorescence in individual cells. Contrary to mutually exclusive expression of antagonistic transcription factors, we observed their ubiquitous co-expression in individual cells at high levels that are distinct from basal-level co-expression during lineage priming. We observed that cytokines are expressed only in a small subpopulation of cells, independent from the expression of transcription factors in these single cells. This cell-to-cell variation in the cytokine expression during the early phase of T helper cell differentiation is significantly larger than in the fully differentiated state. Upon inhibition of cytokine signaling, we observed the classic mutual exclusion of antagonistic transcription factors, thus revealing a weak intracellular network otherwise overruled by the strong signals that emanate from extracellular cytokines. These results suggest that during the early differentiation process CD4 T cells acquire a mixed Th1/Th2 state, instructed by extracellular cytokines. The interplay between extracellular and intracellular signaling components unveiled in Th1/Th2 differentiation may be a common strategy for mammalian cells to buffer against noisy cytokine expression.

 

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