An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

Handle URI:
http://hdl.handle.net/10754/623673
Title:
An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells
Authors:
Ali, Amal Jehad Mohammad; AbuElela, Ayman ( 0000-0002-4529-3156 ) ; Merzaban, Jasmeen S. ( 0000-0002-7276-2907 )
Abstract:
Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Ali AJ, Abuelela AF, Merzaban JS (2017) An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells. Frontiers in Immunology 8. Available: http://dx.doi.org/10.3389/fimmu.2017.00492.
Publisher:
Frontiers Media SA
Journal:
Frontiers in Immunology
KAUST Grant Number:
CRG2_R2_13_MERZ_KAUST_1
Issue Date:
3-May-2017
DOI:
10.3389/fimmu.2017.00492
Type:
Article
ISSN:
1664-3224
Sponsors:
This work was supported by the King Abdullah University of Science and Technology (KAUST) Faculty Baseline Research Funding Program as well as a Competitive Research Grant (CRG2_R2_13_MERZ_KAUST_1) to JM. The authors would like to thank Dr. Samir M. Hamdan for discussions regarding SPR studies and Ms. Samar A. Rostom for her support in the management of the lab. The authors would also like to thank Carolyn Unck from the Academic Writing Services at KAUST for editing the manuscript. In addition, a special thanks to Dr. Aswini K. Panigrahi from the Bioscience Core Lab facility for the mass spectrometry assistance and the rest of the members of the Cell Migration and Signaling Laboratory for their support.
Additional Links:
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00492/full
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorAli, Amal Jehad Mohammaden
dc.contributor.authorAbuElela, Aymanen
dc.contributor.authorMerzaban, Jasmeen S.en
dc.date.accessioned2017-05-22T06:58:02Z-
dc.date.available2017-05-22T06:58:02Z-
dc.date.issued2017-05-03en
dc.identifier.citationAli AJ, Abuelela AF, Merzaban JS (2017) An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells. Frontiers in Immunology 8. Available: http://dx.doi.org/10.3389/fimmu.2017.00492.en
dc.identifier.issn1664-3224en
dc.identifier.doi10.3389/fimmu.2017.00492en
dc.identifier.urihttp://hdl.handle.net/10754/623673-
dc.description.abstractSelectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.en
dc.description.sponsorshipThis work was supported by the King Abdullah University of Science and Technology (KAUST) Faculty Baseline Research Funding Program as well as a Competitive Research Grant (CRG2_R2_13_MERZ_KAUST_1) to JM. The authors would like to thank Dr. Samir M. Hamdan for discussions regarding SPR studies and Ms. Samar A. Rostom for her support in the management of the lab. The authors would also like to thank Carolyn Unck from the Academic Writing Services at KAUST for editing the manuscript. In addition, a special thanks to Dr. Aswini K. Panigrahi from the Bioscience Core Lab facility for the mass spectrometry assistance and the rest of the members of the Cell Migration and Signaling Laboratory for their support.en
dc.publisherFrontiers Media SAen
dc.relation.urlhttp://journal.frontiersin.org/article/10.3389/fimmu.2017.00492/fullen
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCell adhesionen
dc.subjectE-selectinen
dc.subjectPsoriasisen
dc.subjectCD44en
dc.subjectcell migrationen
dc.subjectP-selectin Glycoprotein Ligand-1 (Cd162)en
dc.subjectHematopoietic Cell E- And/or L-selectin Liganden
dc.subjectHuman Activated T-cellsen
dc.titleAn Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cellsen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalFrontiers in Immunologyen
dc.eprint.versionPublisher's Version/PDFen
kaust.authorAli, Amal Jehad Mohammaden
kaust.authorAbuElela, Aymanen
kaust.authorMerzaban, Jasmeen S.en
kaust.grant.numberCRG2_R2_13_MERZ_KAUST_1en
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