Abstract
The evolutionarily conserved Notch signalling pathway regulates the differentiation and function of mature T lymphocytes with major context-dependent consequences in host defence, autoimmunity and alloimmunity. The emerging effects of Notch signalling in T cell responses build upon a more established role for Notch in T cell development. Here, we provide a critical review of this burgeoning literature to make sense of what has been learned so far and highlight the experimental strategies that have been most useful in gleaning physiologically relevant information. We outline the functional consequences of Notch signalling in mature T cells in addition to key specific Notch ligand–receptor interactions and downstream molecular signalling pathways. Our goal is to help clarify future directions for this expanding body of work and the best approaches to answer important open questions.
Highlights
Notch, an evolutionarily conserved cell-to-cell signalling pathway, plays multiple functions at selected stages of innate and adaptive immune cell development, as well as in regulating mature immune cell function
Notch signalling in T cells is a critical regulator of alloimmunity during both solid organ transplant rejection and graftversus-host disease (GVHD) after allogeneic bone marrow transplantation, which we have reviewed elsewhere [82]
We found dramatic protection against GVHD in MHC-mismatched transplants when Notch signalling was blocked in donor T cells via either conditional dominant-negative form of MAML (DNMAML) expression or loss of RBP-Jκ [58,59]
Summary
An evolutionarily conserved cell-to-cell signalling pathway, plays multiple functions at selected stages of innate and adaptive immune cell development, as well as in regulating mature immune cell function. Through its involvement in both developing and mature immune cells, Notch is emerging as a critical actor in host defence and immune pathology. An emerging role of Notch signalling in mature T cells during homeostasis and immune responses in peripheral tissues has come into view. Work has begun to illuminate how cell-type and context-specific Notch signalling shapes T cell immune responses while driving T cell-mediated pathologies. We will review the literature to summarize prior work and to weigh available evidence for how Notch influences mature T cells in the periphery. We aim to provide a clear picture of what has been established in the field and identify larger themes for how Notch functions in mature T cells
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