Unravelling the molecular basis for regulatory T-cell plasticity and loss of function in disease

Clinical & Translational Immunology
Timothy SadlonSimon C Barry

Abstract

Regulatory T cells (Treg) are critical for preventing autoimmunity and curtailing responses of conventional effector T cells (Tconv). The reprogramming of T-cell fate and function to generate Treg requires switching on and off of key gene regulatory networks, which may be initiated by a subtle shift in expression levels of specific genes. This can be achieved by intermediary regulatory processes that include microRNA and long noncoding RNA-based regulation of gene expression. There are well-documented microRNA profiles in Treg and Tconv, and these can operate to either reinforce or reduce expression of a specific set of target genes, including FOXP3 itself. This type of feedforward/feedback regulatory loop is normally stable in the steady state, but can alter in response to local cues or genetic risk. This may go some way to explaining T-cell plasticity. In addition, in chronic inflammation or autoimmunity, altered Treg/Tconv function may be influenced by changes in enhancer-promoter interactions, which are highly cell type-specific. These interactions are impacted by genetic risk based on genome-wide association studies and may cause subtle alterations to the gene regulatory networks controlled by or controlling FOXP3 and its ...Continue Reading

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Citations

Apr 4, 2018·Clinical & Translational Immunology·Kirsten A Ward-Hartstonge, Ajithkumar Vasanthakumar
Oct 3, 2018·The Journal of Clinical Investigation·Sarah A RobertsonLachlan M Moldenhauer
Apr 16, 2019·Frontiers in Immunology·Sarah A RobertsonGustaaf Dekker
Nov 14, 2019·International Journal of Molecular Sciences·Carlo TicconiAsgerally Fazleabas
Oct 15, 2020·Journal of Neuroinflammation·Chiara BurgalettoGiuseppina Cantarella

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Methods Mentioned

BETA
ChIP
immunoprecipitation
iCLIP
genotyping

Software Mentioned

FANTOM
ENCODE
VISTA

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