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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sg-ntu-dr.10356-897142023-02-28T18:47:59Z The functional significance of Talin1 in dendritic cells Lim, Thomas Jun Feng Su I-Hsin School of Biological Sciences DRNTU::Science::Biological sciences 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. Doctor of Philosophy 2018-12-20T23:55:31Z 2019-12-06T17:31:48Z 2018-12-20T23:55:31Z 2019-12-06T17:31:48Z 2018 Thesis Lim, T. J. F. (2018).The functional significance of Talin1 in dendritic cells. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/89714 http://hdl.handle.net/10220/47145 10.32657/10220/47145 en 101 p. application/pdf |
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DRNTU::Science::Biological sciences Lim, Thomas Jun Feng The functional significance of Talin1 in dendritic cells |
description |
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. |
author2 |
Su I-Hsin |
author_facet |
Su I-Hsin Lim, Thomas Jun Feng |
format |
Theses and Dissertations |
author |
Lim, Thomas Jun Feng |
author_sort |
Lim, Thomas Jun Feng |
title |
The functional significance of Talin1 in dendritic cells |
title_short |
The functional significance of Talin1 in dendritic cells |
title_full |
The functional significance of Talin1 in dendritic cells |
title_fullStr |
The functional significance of Talin1 in dendritic cells |
title_full_unstemmed |
The functional significance of Talin1 in dendritic cells |
title_sort |
functional significance of talin1 in dendritic cells |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/89714 http://hdl.handle.net/10220/47145 |
_version_ |
1759857497573687296 |