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The molecular regulation of T helper cell subtype plasticity.

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Unravelling the molecular network of T cells

T helper cells are linked with autoimmune diseases, allergies and asthma. Therefore, reprogramming these cells could serve as a therapeutic approach.

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Helper T lymphocytes are key cells implicated in adaptive immunity. They recognise foreign antigens and differentiate into distinct subsets in response to different pathogens. However, the molecular regulation of this differentiation remains poorly understood. Existing reports rely on conventional transcriptomics based on populations of cells. However, the generated data represent averages over large numbers of cells, without accounting for the distinct cell types within the population. To overcome this limitation, the EU-funded project 'The molecular regulation of T helper cell subtype plasticity' (THPLAST) set out to study immune system dynamics and in particular the process of helper T cell differentiation at the single-cell level. Scientists used a mouse model that mounts a type 2 immune response following infection with the worm N. brasiliensis. Researchers isolated single CD4+ T helper cells from different mouse tissues and subjected them to gene expression analysis. First, they established that their method was sensitive, the error was within an acceptable range, and there was a good overall correlation between mRNA and protein levels. Subsequently, they measured the expression levels of 96 different genes in naive and activated T cells. Activated T cells expressed higher levels of genes implicated in Th2 immunity and in T regulatory cells. Based on gene expression, the profile of the cells could be categorised into three different populations, namely regulatory T cells, follicular Th cells and another previously unidentified subset. The latter population of cells expressed the hormone nuclear receptor RORA and is believed to trigger cytokine secretion and cell activation. These RORA positive cells were mainly localised in peripheral tissues such as the lung and the intestine, underscoring their importance in local immune responses. Taken together, the findings of the THPLAST study contribute to a more complete understanding of the regulatory network involved in T helper cell development. Among the key findings of the study is the identification of cells with inherent plasticity that exhibit the capacity to differentiate into distinct cell subsets in response to extrinsic signals.


T helper cells, adaptive immunity, molecular regulation, plasticity, cell differentiation

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