The functional significance of Talin1 in dendritic cells

Abstract

Skin inflammation caused by foreign pathogens or allergens promotes the activation of skin dendritic cells (DCs) and induces their chemokine-guided migration to the draining lymph nodes. We discovered that talin1, a well-established integrin co-activator, not only regulates the integrin-dependent migration of Langerhans Cells across the epidermal basement membrane, it also regulates the activation of DCs. DC activation was compromised in cells depleted of talin1, resulting in an impeded NFκB activation and a reduction in the expression levels of various pro-inflammatory cytokines. Biochemical analyses reveal that the integrin-binding and activating properties of talin1 are essential for the assembly of TLR4 signalosome, where the interaction between talin1 and MyD88 bridges integrin heterodimers to TLR4. Conversely, TRIF-dependent TLR3 signaling cascade is not affected by the lack of talin1, suggesting that talin1 regulates the MyD88- dependent pathway exclusively. Taken together, our data highlights a novel role of talin1 in TLR4 signaling pathways.