IL-21 protein a key part of immune response to central nervous system infections

Date:
October 6, 2020
Source:
Penn State
Summary:
Researchers now better understand the role of a protein,
interleukin-21 (IL-21), in the immune system response to infections
in the nervous system. The results of their recent study support
further investigation into using IL-21 as a therapeutic agent for
persistent central nervous system infections.



FULL STORY ========================================================================== Researchers at Penn State College of Medicine now better understand the
role of a protein, interleukin-21 (IL-21), in the immune system response
to infections in the nervous system. The results of their recent study
support further investigation into using IL-21 as a therapeutic agent
for persistent central nervous system infections.


==========================================================================
CD4 T cells in the immune system produce IL-21, which is critical for the development of CD8 tissue-resident-memory (TRM) cells during persistent
viral infections of the central nervous system with polyomavirus.

Dr. Aron Lukacher, professor and chair of the Department of Microbiology
and Immunology, said the results, published in Science Immunology,
demonstrate that IL-21 is an important factor in the development
of effective immune responses to chronic infections in the central
nervous system including neurodegenerative HIV-AIDS and progressive
multifocal leukoencephalopathy (PML), a fatal brain infection caused
by JC polyomavirus. PML starts with symptoms including clumsiness,
weakness or difficulty speaking or thinking. As it progresses, patients
may develop dementia, have vision problems and become unable to speak.

Lukacher's lab created an animal model of JC polyomavirus in mice,
called mouse polyomavirus (MuPyV). Their research focuses on strategies
to reduce the harmful effects of MuPyV, with the goal of developing translational approaches to improving outcomes for patients with PML
and other immunocompromising conditions.

Prior research demonstrated that IL-21 is a key part of immune responses
in the body, but the present study investigated the specific mechanisms
and role IL-21 plays in the immune response to infection with MuPyV.

The research team, including medical scientist training program student
Heather Ren, studied mice that were unable to produce sufficient CD4
T-cells and had similar defects in gene expression related to the
development of CD8 TRM cells.

They found that injecting IL-21 into cerebrospinal fluid reduced those deficiencies.

"The use of IL-21 as a therapeutic agent for persistent central nervous
system infections needs further investigation," Lukacher, a researcher at
Penn State Cancer Institute, said. "Whether it needs to be administered directly into the central nervous system or given peripherally, such
as intravenous infusion, will require further testing in our model."
Lukacher said future studies will examine whether giving IL-21 to mice
with persistent MuPyV infection, both under immunocompetent and CD4 T-cell-deficient conditions, may bolster protective antiviral CD8 T cell responses and keep the viral infection in check.


========================================================================== Story Source: Materials provided by Penn_State. Original written by
Zachary Sweger. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Heather M. Ren, Elizabeth M. Kolawole, Mingqiang Ren, Ge Jin,
Colleen S.

Netherby-Winslow, Quinn Wade, Shwetank, Ziaur S. M. Rahman, Brian D.

Evavold, Aron E. Lukacher. IL-21 from high-affinity CD4 T cells
drives differentiation of brain-resident CD8 T cells during
persistent viral infection. Science Immunology, 2020; 5 (51):
eabb5590 DOI: 10.1126/ sciimmunol.abb5590 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201006094549.htm

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