Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling
Talin critically controls integrin-dependent cell migration, but its regulatory role in skin dendritic cells (DCs) during inflammatory responses has not been investigated. Here, we show that talin1 regulates not only integrin-dependent Langerhans cell (LC) migration, but also MyD88-dependent Toll-li...
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| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/147535 https://rupress.org/jem/article/217/8/e20191810/151800/Talin1-controls-dendritic-cell-activation-by |
| _version_ | 1811682517443411968 |
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| author | Lim, Thomas Jun Feng Bunjamin, Maegan Ruedl, Christiane Su, I-hsin |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Lim, Thomas Jun Feng Bunjamin, Maegan Ruedl, Christiane Su, I-hsin |
| author_sort | Lim, Thomas Jun Feng |
| collection | NTU |
| description | Talin critically controls integrin-dependent cell migration, but its regulatory role in skin dendritic cells (DCs) during inflammatory responses has not been investigated. Here, we show that talin1 regulates not only integrin-dependent Langerhans cell (LC) migration, but also MyD88-dependent Toll-like receptor (TLR)–stimulated DC activation. Talin1-deficient LCs failed to exit the epidermis, resulting in reduced LC migration to skin-draining lymph nodes (sdLNs) and defective skin tolerance induction, while talin1-deficient dermal DCs unexpectedly accumulated in the dermis despite their actomyosin-dependent migratory capabilities. Furthermore, talin1-deficient DCs exhibited compromised chemotaxis, NFκB activation, and proinflammatory cytokine production. Mechanistically, talin1 was required for the formation of preassembled TLR complexes in DCs at steady state via direct interaction with MyD88 and PIP5K. Local production of PIP2 by PIP5K then recruited TIRAP to the preassembled complexes, which were required for TLR signalosome assembly during DC activation. Thus, talin1 regulates MyD88-dependent TLR signaling pathways in DCs through a novel mechanism with implications for antimicrobial and inflammatory immune responses. |
| first_indexed | 2024-10-01T03:58:06Z |
| format | Journal Article |
| id | ntu-10356/147535 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:58:06Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1475352021-04-12T01:43:13Z Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling Lim, Thomas Jun Feng Bunjamin, Maegan Ruedl, Christiane Su, I-hsin School of Biological Sciences Science Beta1 Integrin Animal Cell Talin critically controls integrin-dependent cell migration, but its regulatory role in skin dendritic cells (DCs) during inflammatory responses has not been investigated. Here, we show that talin1 regulates not only integrin-dependent Langerhans cell (LC) migration, but also MyD88-dependent Toll-like receptor (TLR)–stimulated DC activation. Talin1-deficient LCs failed to exit the epidermis, resulting in reduced LC migration to skin-draining lymph nodes (sdLNs) and defective skin tolerance induction, while talin1-deficient dermal DCs unexpectedly accumulated in the dermis despite their actomyosin-dependent migratory capabilities. Furthermore, talin1-deficient DCs exhibited compromised chemotaxis, NFκB activation, and proinflammatory cytokine production. Mechanistically, talin1 was required for the formation of preassembled TLR complexes in DCs at steady state via direct interaction with MyD88 and PIP5K. Local production of PIP2 by PIP5K then recruited TIRAP to the preassembled complexes, which were required for TLR signalosome assembly during DC activation. Thus, talin1 regulates MyD88-dependent TLR signaling pathways in DCs through a novel mechanism with implications for antimicrobial and inflammatory immune responses. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) T.J.F. Lim is supported by the A*STAR Graduate Scholarship (AGS). I.S. is supported by the Singapore Ministry of Education (AcRF Tier 1 RG40/13 and RG36/17, MOE2013-T2-2-038 and MOE2017-T2-2-054) and Ministry of Health, National Medical Research Council (NMRC-CBRG/0057/201). 2021-04-12T01:05:46Z 2021-04-12T01:05:46Z 2020 Journal Article Lim, T. J. F., Bunjamin, M., Ruedl, C. & Su, I. (2020). Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling. Journal of Experimental Medicine, 217(8), e20191810-. https://dx.doi.org/10.1084/jem.20191810 0022-1007 https://hdl.handle.net/10356/147535 https://rupress.org/jem/article/217/8/e20191810/151800/Talin1-controls-dendritic-cell-activation-by 10.1084/jem.20191810 8 217 e20191810 en 001125-00001 002222-00001 Journal of Experimental Medicine © 2020 The Author(s). Published by Rockefeller University Press (RUP). All rights reserved. |
| spellingShingle | Science Beta1 Integrin Animal Cell Lim, Thomas Jun Feng Bunjamin, Maegan Ruedl, Christiane Su, I-hsin Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling |
| title | Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling |
| title_full | Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling |
| title_fullStr | Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling |
| title_full_unstemmed | Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling |
| title_short | Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling |
| title_sort | talin1 controls dendritic cell activation by regulating tlr complex assembly and signaling |
| topic | Science Beta1 Integrin Animal Cell |
| url | https://hdl.handle.net/10356/147535 https://rupress.org/jem/article/217/8/e20191810/151800/Talin1-controls-dendritic-cell-activation-by |
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