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High migratory and cytotoxic capability of CD56bright NK cells in a BBB in vitro model

Hu, Chuxuan (2020) MOBN03 20192
Degree Projects in Molecular Biology
Popular Abstract
High Migratory and Cytotoxic Capability of CD56bright NK Cells in a Blood-Brain-Barrier in Vitro Model

The blood brain barrier (BBB) is a tight structure in the Central Nervous System (CNS) that restricts the entry of immune cells. This restriction is regulated by different components such as endothelial cells, tight junction proteins and other cells such as pericytes, astrocytes and neurons. Natural killer (NK) cells have a strong migratory capacity during neurological conditions, such as multiple sclerosis. However, the migratory mechanisms of NK cells in viral infections and other pathologies have been understudied.

The CNS counts with an ingenious system that tightly controls the entry of different cells, especially the immune... (More)
High Migratory and Cytotoxic Capability of CD56bright NK Cells in a Blood-Brain-Barrier in Vitro Model

The blood brain barrier (BBB) is a tight structure in the Central Nervous System (CNS) that restricts the entry of immune cells. This restriction is regulated by different components such as endothelial cells, tight junction proteins and other cells such as pericytes, astrocytes and neurons. Natural killer (NK) cells have a strong migratory capacity during neurological conditions, such as multiple sclerosis. However, the migratory mechanisms of NK cells in viral infections and other pathologies have been understudied.

The CNS counts with an ingenious system that tightly controls the entry of different cells, especially the immune cells. Two natural barriers act as a guard: the blood brain barrier (BBB) and the cerebrospinal fluid barrier (BCFB). Natural killer (NK) cells can defend the organisms from tumors or from virus and bacteria by secreting cytotoxic molecules or by directly killing the infected cells once they invade our bodies. NK cells are commonly classified into CD56bright and CD56dim according to the expression of a molecule called CD56 and their main function is to kill either by releasing molecules needed to call other cells and mount an immune response, or by directly killing their targets. NK cells have a strong capability to migrate from blood to different organs and exert their different functions there. Here, I present a migration story of NK cells through the BBB by means of an in vitro model, using techniques such as measurement of transendothelial electrical resistance, barrier permeability assays and multiparameter flow cytometry.

The BBB in vitro model is constructed using a “filter” or a membrane with little pores that are smaller than the size of a cell, therefore endothelial cells can rest on such membrane and be close with each other forming a tight barrier (see figure). If we want to know the migration capability, cells such as lymphocytes can be added on the top of the membrane. Some cells will remain on the upper compartment and those with high capability to migrate will cross the endothelial barrier and also through the small pores. Therefore, the characteristics of the cells in both compartments can be studied to understand more the migration process.

One of our most striking findings was that among all the lymphocytes studied, the CD56bright NK cell population had a very high capability to cross the barrier. These cells showed a high-activated status and had a higher possibility to defend from the alien invaders by expressing more CD69, granzyme A granzyme B and perforin, which are molecules important in killing. Our results suggest that one of the reasons why CD56bright NK cells are mainly found in solid and lymphoid organs, might be due to their high capability to migrate.



Master’s Degree Project in Molecular Biology 60 credits 2019-2020
Department of Biology, Lund University

Advisor: Dr. Angelica Cuapio Gómez
Center for Infectious Medicine, Karolinska Institutet, Huddinge, Sweden (Less)
Please use this url to cite or link to this publication:
author
Hu, Chuxuan
supervisor
organization
course
MOBN03 20192
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9029321
date added to LUP
2020-09-15 11:40:52
date last changed
2020-09-15 11:40:52
@misc{9029321,
  author       = {{Hu, Chuxuan}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{High migratory and cytotoxic capability of CD56bright NK cells in a BBB in vitro model}},
  year         = {{2020}},
}