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The endothelial diapedesis synapse regulates transcellular migration of human T lymphocytes in a CX3CL1- and SNAP23-dependent manner. / Schoppmeyer, Rouven; van Steen, Abraham C. I.; Kempers, Lanette; Timmerman, Anne L.; Nolte, Martijn A.; Hombrink, Pleun; van Buul, Jaap D.

In: Cell reports, Vol. 38, No. 3, 110243, 18.01.2022.

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@article{a50cc4bea5974ea28916074aa8bb374f,
title = "The endothelial diapedesis synapse regulates transcellular migration of human T lymphocytes in a CX3CL1- and SNAP23-dependent manner",
abstract = "Understanding how cytotoxic T lymphocytes (CTLs) efficiently leave the circulation to target cancer cells or contribute to inflammation is of high medical interest. Here, we demonstrate that human central memory CTLs cross the endothelium in a predominantly paracellular fashion, whereas effector and effector memory CTLs cross the endothelium preferably in a transcellular fashion. We find that effector CTLs show a round morphology upon adhesion and induce a synapse-like interaction with the endothelium where ICAM-1 is distributed at the periphery. Moreover, the interaction of ICAM-1:β2integrin and endothelial-derived CX3CL1:CX3CR1 enables transcellular migration. Mechanistically, we find that ICAM-1 clustering recruits the SNARE-family protein SNAP23, as well as syntaxin-3 and -4, for the local release of endothelial-derived chemokines like CXCL1/8/10. In line, silencing of endothelial SNAP23 drives CTLs across the endothelium in a paracellular fashion. In conclusion, our data suggest that CTLs trigger local chemokine release from the endothelium through ICAM-1-driven signals driving transcellular migration.",
keywords = "CD8 T cells, chemokines, cytotoxic T cells, diapedesis synapse, endothelium, inflammation, membrane protrusions, transcellular, transmigration",
author = "Rouven Schoppmeyer and {van Steen}, {Abraham C. I.} and Lanette Kempers and Timmerman, {Anne L.} and Nolte, {Martijn A.} and Pleun Hombrink and {van Buul}, {Jaap D.}",
note = "Funding Information: This work was supported by LSBR grant #1649 and #1820 (A.C.I.v.S. and L.K.), and ZonMW NWO Vici grant #91819632 (R.S. and J.D.v.B.). Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2022",
month = jan,
day = "18",
doi = "10.1016/j.celrep.2021.110243",
language = "English",
volume = "38",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - The endothelial diapedesis synapse regulates transcellular migration of human T lymphocytes in a CX3CL1- and SNAP23-dependent manner

AU - Schoppmeyer, Rouven

AU - van Steen, Abraham C. I.

AU - Kempers, Lanette

AU - Timmerman, Anne L.

AU - Nolte, Martijn A.

AU - Hombrink, Pleun

AU - van Buul, Jaap D.

N1 - Funding Information: This work was supported by LSBR grant #1649 and #1820 (A.C.I.v.S. and L.K.), and ZonMW NWO Vici grant #91819632 (R.S. and J.D.v.B.). Publisher Copyright: © 2021 The Authors

PY - 2022/1/18

Y1 - 2022/1/18

N2 - Understanding how cytotoxic T lymphocytes (CTLs) efficiently leave the circulation to target cancer cells or contribute to inflammation is of high medical interest. Here, we demonstrate that human central memory CTLs cross the endothelium in a predominantly paracellular fashion, whereas effector and effector memory CTLs cross the endothelium preferably in a transcellular fashion. We find that effector CTLs show a round morphology upon adhesion and induce a synapse-like interaction with the endothelium where ICAM-1 is distributed at the periphery. Moreover, the interaction of ICAM-1:β2integrin and endothelial-derived CX3CL1:CX3CR1 enables transcellular migration. Mechanistically, we find that ICAM-1 clustering recruits the SNARE-family protein SNAP23, as well as syntaxin-3 and -4, for the local release of endothelial-derived chemokines like CXCL1/8/10. In line, silencing of endothelial SNAP23 drives CTLs across the endothelium in a paracellular fashion. In conclusion, our data suggest that CTLs trigger local chemokine release from the endothelium through ICAM-1-driven signals driving transcellular migration.

AB - Understanding how cytotoxic T lymphocytes (CTLs) efficiently leave the circulation to target cancer cells or contribute to inflammation is of high medical interest. Here, we demonstrate that human central memory CTLs cross the endothelium in a predominantly paracellular fashion, whereas effector and effector memory CTLs cross the endothelium preferably in a transcellular fashion. We find that effector CTLs show a round morphology upon adhesion and induce a synapse-like interaction with the endothelium where ICAM-1 is distributed at the periphery. Moreover, the interaction of ICAM-1:β2integrin and endothelial-derived CX3CL1:CX3CR1 enables transcellular migration. Mechanistically, we find that ICAM-1 clustering recruits the SNARE-family protein SNAP23, as well as syntaxin-3 and -4, for the local release of endothelial-derived chemokines like CXCL1/8/10. In line, silencing of endothelial SNAP23 drives CTLs across the endothelium in a paracellular fashion. In conclusion, our data suggest that CTLs trigger local chemokine release from the endothelium through ICAM-1-driven signals driving transcellular migration.

KW - CD8 T cells

KW - chemokines

KW - cytotoxic T cells

KW - diapedesis synapse

KW - endothelium

KW - inflammation

KW - membrane protrusions

KW - transcellular

KW - transmigration

UR - http://www.scopus.com/inward/record.url?scp=85122833169&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.110243

DO - 10.1016/j.celrep.2021.110243

M3 - Article

C2 - 35045291

VL - 38

JO - Cell reports

JF - Cell reports

SN - 2211-1247

IS - 3

M1 - 110243

ER -

ID: 21307161