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Integrin Crosstalk in the Upstream M...

Kim, Hyun Ji.

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Integrin Crosstalk in the Upstream Migration of CD4+ T Lymphocytes.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Integrin Crosstalk in the Upstream Migration of CD4+ T Lymphocytes./
Author:	Kim, Hyun Ji.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	211 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-11, Section: B.
Contained By:	Dissertations Abstracts International82-11B.
Subject:	Bioengineering. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28319688
ISBN:	9798738642333

Integrin Crosstalk in the Upstream Migration of CD4+ T Lymphocytes.
Kim, Hyun Ji.

Integrin Crosstalk in the Upstream Migration of CD4+ T Lymphocytes. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 211 p.

Source: Dissertations Abstracts International, Volume: 82-11, Section: B.

Thesis (Ph.D.)--University of Pennsylvania, 2021.

This item must not be sold to any third party vendors.

Leukocytes travel between different tissues, ranging from an inflamed site, bone marrow to lymph node after hematopoiesis for further development and maturation, to another tissue, through the vasculature. To efficiently reach the destination, circulating leukocytes in the blood stream must be able to adhere and exit the circulation. Recently, T lymphocytes have been shown to distinguish the direction of shear flow and migrate in a direction that is determined by adhesion molecules on the surface. T lymphocytes with LFA-1-ICAM-1 interaction migrate upstream (i.e. in the opposite direction of shear flow), and those with VLA-4-VCAM-1 binding migrate downstream (i.e. with the direction of flow). In the first aim, we study the crosstalk of LFA-1 and VLA-4 integrins in the upstream migration. We showed that while LFA-1 and VLA-4 mediated migration independently show very different directional response, LFA-1 and VLA-4 together potentiates the upstream migration during and post flow. The persistent direction of migration is mediated by PI3K. We uncover the intracellular signaling mechanism responsible for the upstream migration of CD4+ T lymphocytes with mice models in collaboration with Dr. Janis K. Burkhardt at Children's Hospital of Philadelphia. We found that, downstream of LFA-1, Crk and c-Cbl are key in the upstream direction. Lastly, in the third aim we investigate how the substrate mechanics affect the motility of CD4+ T lymphocytes under static and flow conditions. Specifically, we reported that while LFA-1-mediated migration under static conditions showed stiffness-dependent motility, the upstream migration under flow was unaffected. Together, we provide more insight to understanding the mechanism of the upstream migration.

ISBN: 9798738642333Subjects--Topical Terms:

657580
Bioengineering.
Subjects--Index Terms:

Integrins

Integrin Crosstalk in the Upstream Migration of CD4+ T Lymphocytes.
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100 1 $a Kim, Hyun Ji. $3 3556726
245 1 0 $a Integrin Crosstalk in the Upstream Migration of CD4+ T Lymphocytes.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 211 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-11, Section: B.
500 $a Advisor: Hammer, Daniel A.
502 $a Thesis (Ph.D.)--University of Pennsylvania, 2021.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be sold to any third party vendors.
520 $a Leukocytes travel between different tissues, ranging from an inflamed site, bone marrow to lymph node after hematopoiesis for further development and maturation, to another tissue, through the vasculature. To efficiently reach the destination, circulating leukocytes in the blood stream must be able to adhere and exit the circulation. Recently, T lymphocytes have been shown to distinguish the direction of shear flow and migrate in a direction that is determined by adhesion molecules on the surface. T lymphocytes with LFA-1-ICAM-1 interaction migrate upstream (i.e. in the opposite direction of shear flow), and those with VLA-4-VCAM-1 binding migrate downstream (i.e. with the direction of flow). In the first aim, we study the crosstalk of LFA-1 and VLA-4 integrins in the upstream migration. We showed that while LFA-1 and VLA-4 mediated migration independently show very different directional response, LFA-1 and VLA-4 together potentiates the upstream migration during and post flow. The persistent direction of migration is mediated by PI3K. We uncover the intracellular signaling mechanism responsible for the upstream migration of CD4+ T lymphocytes with mice models in collaboration with Dr. Janis K. Burkhardt at Children's Hospital of Philadelphia. We found that, downstream of LFA-1, Crk and c-Cbl are key in the upstream direction. Lastly, in the third aim we investigate how the substrate mechanics affect the motility of CD4+ T lymphocytes under static and flow conditions. Specifically, we reported that while LFA-1-mediated migration under static conditions showed stiffness-dependent motility, the upstream migration under flow was unaffected. Together, we provide more insight to understanding the mechanism of the upstream migration.
590 $a School code: 0175.
650 4 $a Bioengineering. $3 657580
650 4 $a Chemical engineering. $3 560457
650 4 $a Cellular biology. $3 3172791
653 $a Integrins
653 $a LFA-1
653 $a Matrix stiffness
653 $a PI3K
653 $a Shear flow
653 $a T lymphocytes
690 $a 0202
690 $a 0542
690 $a 0379
710 2 $a University of Pennsylvania. $b Chemical and Biomolecular Engineering. $3 2101616
773 0 $t Dissertations Abstracts International $g 82-11B.
790 $a 0175
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28319688