Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function

Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function

Bibliographic Details
Main Author: Briercheck, Edward Lloyd
Language:English
Published: The Ohio State University / OhioLINK 2013
Subjects:
Biology
Medicine
Oncology
Immunology
Natural Killer Cells Innate Immunity Phosphatase and Tensin Homologue Deleted on Chromosome Ten PTEN Immunotherapy
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1373363209
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu13733632092021-08-03T05:24:39Z Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function Briercheck, Edward Lloyd Biology Medicine Oncology Immunology Natural Killer Cells Innate Immunity Phosphatase and Tensin Homologue Deleted on Chromosome Ten PTEN Immunotherapy Human natural killer (NK) cells are CD56+CD3- large granular lymphocytes of the innate immune system which are characterized by the ability to both directly kill and initiate an immune response to virally infected or malignantly transformed cells. Human NK cells in peripheral blood can be divided into two developmentally and functionally distinct subsets based upon surface expression of CD56. In contrast to the more mature CD56dim NK cell, the less mature CD56bright NK cell is unable to kill malignant cells at rest. We sought to determine the mechanism of this difference in cytolytic activity by exploring changes in gene expression between CD56bright NK cells and CD56dim NK cells. We observed that CD56bright NK cells showed a ~5 fold increase in PTEN protein expression over CD56dim NK cells. Human and murine NK cells overexpressing PTEN demonstrated decreased cytolytic activity and IFN-¿ secretion, with concurrent decreases in their downstream (MAPK and AKT) targets that are critical for cytolysis. Paradoxically, human NK cells with near complete PTEN knockdown also showed decreased cytolytic activity despite elevations in AKT and MAPK. Confocal microscopy revealed that near complete PTEN knockdown results in a disruption of the NK cell’s ability to organize immunological synapse components including decreased adhesion, decreased polarization of the microtubule organizing center toward the target cell and decrease in coalescence of cytolytic granules. Thus, PTEN is differentially expressed in mature human NK cell subsets and our studies suggest it must be expressed at an optimum level to maximize NK cytolytic activity. 2013-09-03 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1373363209 http://rave.ohiolink.edu/etdc/view?acc_num=osu1373363209 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biology
Medicine
Oncology
Immunology
Natural Killer Cells Innate Immunity Phosphatase and Tensin Homologue Deleted on Chromosome Ten PTEN Immunotherapy
spellingShingle Biology
Medicine
Oncology
Immunology
Natural Killer Cells Innate Immunity Phosphatase and Tensin Homologue Deleted on Chromosome Ten PTEN Immunotherapy
Briercheck, Edward Lloyd
Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function
author Briercheck, Edward Lloyd
author_facet Briercheck, Edward Lloyd
author_sort Briercheck, Edward Lloyd
title Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function
title_short Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function
title_full Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function
title_fullStr Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function
title_full_unstemmed Elucidation of the Mechanism by which Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) Regulates Natural Killer Cell Function
title_sort elucidation of the mechanism by which phosphatase and tensin homologue deleted on chromosome ten (pten) regulates natural killer cell function
publisher The Ohio State University / OhioLINK
publishDate 2013
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1373363209
work_keys_str_mv AT briercheckedwardlloyd elucidationofthemechanismbywhichphosphataseandtensinhomologuedeletedonchromosometenptenregulatesnaturalkillercellfunction
_version_ 1719419836987080704

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