Overview of Integrin Signaling in the Immune System

Abstract

It has been well established that integrins mediate cell-cell and cell-matrix adhesion and play crucial roles in the immune system such as leukocyte-endothelium interactions, immune synapse formation, and effector functions. Since the discovery that integrins undergo dynamic changes of adhesive activities in response to external stimuli, intensive studies have been conducted to elucidate the signaling events that control the activation of integrins (inside-out signaling) and signaling events from the induced integrin-dependent adhesion (outside-in signaling). The molecular characterization of these signaling pathways highlights the importance of integrins as bidirectional signaling receptors. The characteristics of integrin signaling are best exemplified in the immune system. This chapter highlights the recent studies of intracellular signaling pathways that regulate integrins in immunological contexts.

The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance

“…In support of this model, TCR-triggered binding of LFA-1 to ICAM-1 led to enhanced expression of Bcl-6 in vitro compared to CD28-mediated costimulation. However, deletion of Talin-1, a cytosolic protein recruited to the β2 integrin subunit following inside-out activation and required for acquisition of the high-affinity conformation of LFA-1, compromised Bcl-6 expression in vitro and Tfh cell differentiation in vivo, but did not impact the activation of T cells and their ability to commit to other Teff lineages such as Gata3 + Th2 cells (Kinashi, 2012). As Talin-1 is additionally required for the high-affinity conformation of β1 and β3 integrins (Petrich et al, 2007), we cannot exclude the possibility that loss of activity in these integrins contribute to the phenotype observed in our in vivo experiments.…”

Sequestosome1/p62: A regulator of redox-sensitive voltage-activated potassium channels, arterial remodeling, inflammation, and neurite outgrowth

“…Activation of integrin through diverse receptors is essential for T cell migration and the formation of an immunological synapse [134,135]. Actually, TCR activation rapidly upregulates β1-integrinmediated adhesion to fibronectin and migration [136,137].…”

“…Lck is expressed in T lymphocytes and neurons including PC12 cells. Activation of T lymphocytes through TCR rapidly upregulates β1-integrin-mediated adhesion to fibronectin and migration [134,135]. SQSTM1 contributes Th2 skewed differentiation and activation [111].…”

CD11b‐deficient mice exhibit an increased severity in the late phase of antibody transfer‐induced experimental epidermolysis bullosa acquisita

“…[1,2] Due to its array of functions, the role of CD11b in immune-related diseases, for example autoimmune disorders, is heterogeneous and diverse. By investigating corresponding knockout mice, the role of CD11b in various experimental models of autoimmune diseases has been studied, and diverging results have been reported.…”