Please use this identifier to cite or link to this item: doi:10.22028/D291-30518
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Title: Human profilin 1 is a negative regulator of CTL mediated cell-killing and migration
Author(s): Schoppmeyer, Rouven
Zhao, Renping
Cheng, He
Hamed, Mohamed
Liu, Chen
Zhou, Xiao
Schwarz, Eva C.
Zhou, Yan
Knörck, Arne
Schwär, Gertrud
Ji, Shunrong
Liu, Liang
Long, Jiang
Helms, Volkhard
Hoth, Markus
Yu, Xianjun
Qu, Bin
Language: English
Title: European journal of immunology
Volume: 47
Issue: 9
Startpage: 1562
Endpage: 1572
Publisher/Platform: Wiley
Year of Publication: 2017
Publikation type: Journal Article
Abstract: The actin-binding protein profilin1 (PFN1) plays a central role in actin dynamics, which is essential for cytotoxic T lymphocyte (CTL) functions. The functional role of PFN1 in CTLs, however still remains elusive. Here, we identify PFN1 as the only member of the profilin family expressed in primary human CD8+ T cells. Using in vitro assays, we find that PFN1 is a negative regulator of CTL-mediated elimination of target cells. Furthermore, PFN1 is involved in activation-induced lytic granule (LG) release, CTL migration and modulation of actin structures at the immunological synapse (IS). During CTL migration, PFN1 modulates the velocity, protrusion formation patterns and protrusion sustainability. In contrast, PFN1 does not significantly affect migration persistence and the rates of protrusion emergence and retraction. Under in vitro conditions mimicking a tumor microenvironment, we show that PFN1 downregulation promotes CTL invasion into a 3D matrix, without affecting the viability of CTLs in a hydrogen peroxide-enriched microenvironment. Highlighting its potential relevance in cancer, we find that in pancreatic cancer patients, PFN1 expression is substantially decreased in peripheral CD8+ T cells. Taken together, we conclude that PFN1 is a negative regulator for CTL-mediated cytotoxicity and may have an impact on CTL functionality in a tumor-related context.
DOI of the first publication: 10.1002/eji.201747124
URL of the first publication:
Link to this record: hdl:20.500.11880/28894
ISSN: 0014-2980
Date of registration: 20-Mar-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Volkhard Helms
Collections:Die Universitätsbibliographie

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