Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.615371
Keywords
autoimmunity; diabetes; immunoregulation; T cell receptor (TCR) signaling; T cell differentiation
Categories
Funding
- National Institutes of Health [R01DK100256, R01AI139475, R01AI141631, R21AI115752, T32AI007273]
- American Diabetes Association [1-18-PDF-108]
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TCR signaling plays a crucial role in the development of T cells and the formation of self-reactive T cells, particularly in type 1 diabetes.
T cell receptor (TCR) signaling influences multiple aspects of CD4(+) and CD8(+) T cell immunobiology including thymic development, peripheral homeostasis, effector subset differentiation/function, and memory formation. Additional T cell signaling cues triggered by co-stimulatory molecules and cytokines also affect TCR signaling duration, as well as accessory pathways that further shape a T cell response. Type 1 diabetes (T1D) is a T cell-driven autoimmune disease targeting the insulin producing beta cells in the pancreas. Evidence indicates that dysregulated TCR signaling events in T1D impact the efficacy of central and peripheral tolerance-inducing mechanisms. In this review, we will discuss how the strength and nature of TCR signaling events influence the development of self-reactive T cells and drive the progression of T1D through effects on T cell gene expression, lineage commitment, and maintenance of pathogenic anti-self T cell effector function.
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