New Publication: IL7 receptor signaling in T cells: A mathematical modeling perspective

Interleukin-7 (IL7) plays a non-redundant role in T cell survival and homeostasis, which is illustrated in the severe T cell lymphopenia of IL7-de cient mice, or demonstrated in animals or humans that lack expression of either the IL7Ra or gamma-c chain, the two sub-units that constitute the functional IL7 receptor. Remarkably, IL7 is not expressed by T cells themselves, but produced in limited amounts by radio-resistant stromal cells. Thus, T cells need to constantly compete for IL7 to survive. How T cells maintain homeostasis and further maximise the size of the peripheral T cell pool in face of such competition are important questions that have fascinated both immunologists and mathematicians for a long time. Exceptionally, IL7 down-regulates expression of its own receptor, so that IL7-signalled T cells do not consume IL7, and the remaining IL7 can be shared amongst unsignalled T cells. Such an altruistic behaviour of the IL7Ra chain is quite unique among members of the c cytokine receptor family. However, the consequences of this altruistic behaviour at the single cell and the population levels are less understood and require further investigations. In this regard, mathematical modelling of how a limited resource can be shared, while maintaining the clonal diversity of the T cell pool, can help dechipher the molecular or cellular mechanisms that regulate T cell homeostasis. Thus, the current review aims to provide a mathematical modelling perspective of IL7-dependent T cell homeostasis at the molecular, cellular and population levels, in the context of recent advances in our understanding of the IL7 biology.

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