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Title: Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling
Authors: Lim, Thomas Jun Feng
Bunjamin, Maegan
Ruedl, Christiane
Su, I-hsin
Keywords: Science
Issue Date: 2020
Source: 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-.
Project: 001125-00001
Journal: Journal of Experimental Medicine
Abstract: 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.
ISSN: 0022-1007
DOI: 10.1084/jem.20191810
Rights: © 2020 The Author(s). Published by Rockefeller University Press (RUP). All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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