ADD beefier background section on integrin pathways

This commit is contained in:
Nathan Dwarshuis 2021-08-01 13:17:53 -04:00
parent a80c8f07d8
commit adb80cb94e
2 changed files with 132 additions and 4 deletions

View File

@ -1400,6 +1400,96 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
publisher = {Springer Science and Business Media {LLC}}, publisher = {Springer Science and Business Media {LLC}},
} }
@Article{Dustin2001,
author = {Michael L Dustin and Antonin R de Fougerolles},
journal = {Current Opinion in Immunology},
title = {Reprograming T cells: the role of extracellular matrix in coordination of T cell activation and migration},
year = {2001},
month = {jun},
number = {3},
pages = {286--290},
volume = {13},
doi = {10.1016/s0952-7915(00)00217-x},
publisher = {Elsevier {BV}},
}
@Article{Ebnet1996,
author = {Klaus Ebnet and Eric P. Kaldjian and Arthur O. Anderson and Stephen Shaw},
journal = {Annual Review of Immunology},
title = {{ORCHESTRATED} {INFORMATION} {TRANSFER} {UNDERLYING} {LEUKOCYTE} {ENDOTHELIAL} {INTERACTIONS}},
year = {1996},
month = {apr},
number = {1},
pages = {155--177},
volume = {14},
doi = {10.1146/annurev.immunol.14.1.155},
publisher = {Annual Reviews},
}
@Article{Gunzer2000,
author = {Matthias Gunzer and Angelika Schäfer and Stefan Borgmann and Stephan Grabbe and Kurt S. Zänker and Eva-Bettina Bröcker and Eckhart Kämpgen and Peter Friedl},
journal = {Immunity},
title = {Antigen Presentation in Extracellular Matrix},
year = {2000},
month = {sep},
number = {3},
pages = {323--332},
volume = {13},
doi = {10.1016/s1074-7613(00)00032-7},
publisher = {Elsevier {BV}},
}
@Article{Aoudjit2000,
author = {Aoudjit, F. and Vuori, K.},
journal = {Blood},
title = {Engagement of the alpha2beta1 integrin inhibits Fas ligand expression and activation-induced cell death in T cells in a focal adhesion kinase-dependent manner.},
year = {2000},
issn = {0006-4971},
month = mar,
pages = {2044--2051},
volume = {95},
abstract = {T-cell receptor (TCR)-mediated apoptosis, also known as activation-induced cell death (AICD), plays an important role in the control of immune response and in the development of T-cell repertoire. Mechanistically, AICD has been largely attributed to the interaction of Fas ligand (Fas-L) with its cell surface receptor Fas in activated T cells. Signal transduction mediated by the integrin family of cell adhesion receptors has been previously shown to modulate apoptosis in a number of different cell types; in T cells, integrin signaling is known to be important in cellular response to antigenic challenge by providing a co-stimulatory signal for TCR. In this study we demonstrate that signaling via the collagen receptor alpha2beta1 integrin specifically inhibits AICD by inhibiting Fas-L expression in activated Jurkat T cells. Engagement of the alpha2beta1 integrin with monoclonal antibodies or with type I collagen, a cognate ligand for alpha2beta1, reduced anti-CD3 and PMA/ionomycin-induced cell death by 30% and 40%, respectively, and the expression of Fas-L mRNA by 50%. Further studies indicated that the alpha2beta1-mediated inhibition of AICD and Fas-L expression required the focal adhesion kinase FAK, a known component in the integrin signaling pathways. These results suggest a role for the alpha2beta1 integrin in the control of homeostasis of immune response and T-cell development. (Blood. 2000;95:2044-2051)},
chemicals = {CD3 Complex, Cell Adhesion Molecules, FASLG protein, human, Fas Ligand Protein, Integrins, Ionophores, Membrane Glycoproteins, Protein Synthesis Inhibitors, RNA, Messenger, Receptors, Collagen, Ionomycin, Collagen, Cycloheximide, FAK-related nonkinase, Protein-Tyrosine Kinases, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, PTK2 protein, human, Tetradecanoylphorbol Acetate},
citation-subset = {AIM, IM},
completed = {2000-04-07},
country = {United States},
issn-linking = {0006-4971},
issue = {6},
keywords = {Apoptosis; CD3 Complex, metabolism; Cell Adhesion Molecules, metabolism; Cell Death; Collagen, metabolism; Cycloheximide, pharmacology; DNA Fragmentation; Fas Ligand Protein; Flow Cytometry; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Integrins, metabolism; Ionomycin, pharmacology; Ionophores, pharmacology; Jurkat Cells; Membrane Glycoproteins, metabolism; Plasmids; Protein Synthesis Inhibitors, pharmacology; Protein-Tyrosine Kinases, metabolism; RNA, Messenger, metabolism; Receptors, Collagen; Signal Transduction; T-Lymphocytes, metabolism, pathology; Tetradecanoylphorbol Acetate, pharmacology; Transfection},
nlm-id = {7603509},
owner = {NLM},
pii = {S0006-4971(20)66967-1},
pmid = {10706873},
pubmodel = {Print},
pubstate = {ppublish},
revised = {2021-02-16},
}
@Article{Hemler1990,
author = {Hemler, M. E.},
journal = {Annual review of immunology},
title = {VLA proteins in the integrin family: structures, functions, and their role on leukocytes.},
year = {1990},
issn = {0732-0582},
pages = {365--400},
volume = {8},
nasa = {90262672},
chemicals = {Integrins, Receptors, Very Late Antigen},
citation-subset = {IM, S},
completed = {1990-07-02},
country = {United States},
doi = {10.1146/annurev.iy.08.040190.002053},
issn-linking = {0732-0582},
keywords = {Animals; Cell Adhesion; Extracellular Matrix, physiology; Humans; Integrins, biosynthesis, physiology; Leukocytes, physiology; Receptors, Very Late Antigen, biosynthesis, physiology; Structure-Activity Relationship},
nlm-id = {8309206},
owner = {NLM},
pmid = {2188667},
pubmodel = {Print},
pubstate = {ppublish},
references = {212},
revised = {2021-01-02},
}
@Comment{jabref-meta: databaseType:bibtex;} @Comment{jabref-meta: databaseType:bibtex;}
@Comment{jabref-meta: grouping: @Comment{jabref-meta: grouping:

View File

@ -586,10 +586,12 @@ under close cell-cell contact via \glspl{apc} such as \glspl{dc}, which present
peptide-\glspl{mhc} to T cells as well as a variety of other costimulatory peptide-\glspl{mhc} to T cells as well as a variety of other costimulatory
signals. These close quarters allow for efficient autocrine/paracrine signaling signals. These close quarters allow for efficient autocrine/paracrine signaling
among the expanding T cells, which secrete gls{il2} and other cytokines to among the expanding T cells, which secrete gls{il2} and other cytokines to
assist their own growth. Additionally, the lymphoid tissues are comprised of assist their own growth.
\gls{ecm} components such as collagen, which provide signals to upregulate
proliferation, cytokine production, and pro-survival pathways\cite{Gendron2003, % Additionally, the lymphoid tissues are comprised of
Ohtani2008, Boisvert2007, Ben-Horin2004}. % \gls{ecm} components such as collagen, which provide signals to upregulate
% proliferation, cytokine production, and pro-survival pathways\cite{Gendron2003,
% Ohtani2008, Boisvert2007, Ben-Horin2004}.
A variety of solutions have been proposed to make the T cell expansion process A variety of solutions have been proposed to make the T cell expansion process
more physiological. One strategy is to use modified feeder cell cultures to more physiological. One strategy is to use modified feeder cell cultures to
@ -629,6 +631,42 @@ cells to interact with the \glspl{mab} relative to beads; this may better
emulate the large contact surface area that occurs between T cells and emulate the large contact surface area that occurs between T cells and
\glspl{dc}. \glspl{dc}.
\subsection*{integrins and T cell signaling}
Because the microcarriers used in this work are derived from collagen, one key
question is how these collagen domains may interact with the T cells during
culture. This question is further explored in \cref{aim2b}.
T cells naturally expand in the lymph nodes which have an \gls{ecm} composed of
collagen\cite{Dustin2001, Ebnet1996, Ohtani2008}. Despite this, T cells don't
interact with collagen fibers in the lymph node as the collagen fibers are
sheathed with stromal fibroblasts\cite{Dustin2001, Ebnet1996}. However, the
\gls{ecm} of peripheral tissues is dense with exposed collagen fibers are
available to interact with T cells. Furthermore, T cells have been shown
\invitro{} to crawl along collagen fibers in the presence of \glspl{apc},
facilitating short encounters with \glspl{apc}\cite{Gunzer2000}. While this may
not be ideal \invivo{} due to the lack of cumulative signal received by
\glspl{apc}\cite{Dustin2001}, it may be advantageous to include collagen domains
\invitro{} as the mode of activation is not specific to any given clone.
The major surface receptors for collagen are \gls{a2b1} and
\gls{a2b2}\cite{Dustin2001, Hemler1990}. These receptors are not expressed on
naive T cells and thus presence and stimulation of collagen alone is not
sufficient to cause activation or expansion of T cells\cite{Hemler1990}. These
receptors have been shown to lead to a number of functions that may be useful in
the context of T cell expansion. First, they have been shown to act in a
costimulatory manner which leads to increased proliferation\cite{Rao2000}.
Furthermore, \gls{a2b1} and \gls{a2b2} have been shown to protect Jurkat cells
against Fas-mediated apoptosis in the presence of collagen I\cite{Aoudjit2000,
Gendron2003}. Finally, these receptors have been shown to increase \gls{ifng}
production \invitro{} when T cells derived from human \glspl{pbmc} are
stimulated in the presence of collagen I\cite{Boisvert2007}.
% TODO there are other receptors I could name here that were not explored
% Other integrins that interact with the environment include a4b1, which interacts
% with fibronectin and has been shown to lead to higher IL2 production (Iwata et
% al 2000).
\subsection*{strategies to optimize cell manufacturing} \subsection*{strategies to optimize cell manufacturing}
The \gls{dms} system has a number of parameters that can be optimized, and a The \gls{dms} system has a number of parameters that can be optimized, and a