The functional significance of Talin1 in dendritic cells
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...
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| Other Authors: | |
| Format: | Theses and Dissertations |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/89714 http://hdl.handle.net/10220/47145 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | 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. |
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