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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Main Author: Lim, Thomas Jun Feng
Other Authors: Su I-Hsin
Format: Theses and Dissertations
Language:English
Published: 2018
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Online Access:https://hdl.handle.net/10356/89714
http://hdl.handle.net/10220/47145
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Institution: Nanyang Technological University
Language: English
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spelling 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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle 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
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