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

October 05, 2020

HERSHEY, Pa. -- 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.
-end-
Ge Jin, Colleen S. Netherby-Winslow, Quinn Wade, Shwetank and Ziaur Rahman of Penn State College of Medicine; Elizabeth M. Kolawole and Brian Evavold of the University of Utah; and Mingqiang Ren of the Uniformed Services University also contributed to this research.

The National Institutes of Health supported this research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The Penn State College of Medicine Finkelstein Memorial Student Research Award also supported this research. The authors declare no conflict of interest.

Penn State

Related Immune Response Articles from Brightsurf:

Boosting chickens' own immune response could curb disease
Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.

Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.

Children's immune response more effective against COVID-19
Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept.

Which immune response could cause a vaccine against COVID-19?
Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition.

Obesity may alter immune system response to COVID-19
Obesity may cause a hyperactive immune system response to COVID-19 infection that makes it difficult to fight off the virus, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.

Immune response to Sars-Cov-2 following organ transplantation
Even patients with suppressed immune systems can achieve a strong immune response to Sars-Cov-2.

'Relaxed' T cells critical to immune response
Rice University researchers model the role of relaxation time as T cells bind to invaders or imposters, and how their ability to differentiate between the two triggers the body's immune system.

A novel mechanism that triggers a cellular immune response
Researchers at Baylor College of Medicine present comprehensive evidence that supports a novel trigger for a cell-mediated response and propose a mechanism for its action.

Platelets exacerbate immune response
Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes.

How to boost immune response to vaccines in older people
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy ageing for an ageing population.

Read More: Immune Response News and Immune Response Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.