Maintaining immune balance involves an unconventional mechanism of T cell regulation

July 3, 2013, St. Jude Children's Research Hospital

New findings from St. Jude Children's Research Hospital reveal an unconventional control mechanism involved in the production of specialized T cells that play a critical role in maintaining immune system balance. The research appears in the current online edition of the scientific journal Nature.

The work focused on known as regulatory T cells. These cells are crucial for a balanced immune response. Regulatory T cells suppress other immune system components in order to protect healthy tissue from misguided immune attacks or to prevent runaway inflammation.

St. Jude researchers showed that a molecular complex called mTORC1 uses an unconventional process to serve as a rheostat, controlling the supply and function of regulatory T cells. Loss of mTORC1 activity impairs the regulatory T cells that suppress the immune system's . The mTORC1 complex is part of the mTOR pathway, which was thought to inhibit rather than promote the number and function of regulatory T cells.

"These results challenge the prior view of the mTOR pathway as an inhibitor of these key and highlight the role of the mTORC1 complex in regulating the T cells that are vital for controlling inflammation," said Hongbo Chi, Ph.D., an associate member of the St. Jude Department of Immunology and the paper's corresponding author.

The findings also identified the mechanism mTORC1 uses in programming regulatory T cells to function as immune suppressors. Chi said the results should aid efforts to develop for use in or for treatment of autoimmune disorders.

For this study, researchers used specially bred mice to explore the mTOR pathway's role in the function of regulatory T cells. Investigators demonstrated mTORC1's importance by selectively deleting genes that carry instructions for making key elements of mTORC1 and a related complex. The deletion that targeted mTORC1 resulted in dramatically reduced immune suppression by regulatory T cells and the mice rapidly developed a fatal inflammatory disorder.

Researchers also showed that mTORC1 works by integrating signals from two immune receptors on the cell surface with cholesterol metabolism. With the right input, mTORC1 promoted production of regulatory T cells and cemented their role as suppressors of immune activity.

In another twist, investigators linked that suppressive function to cholesterol and lipid metabolism. Rather than relying on more conventional strategies of immune regulation, researchers showed how regulatory T cells depend on the metabolic pathway to control production of molecules CTLA4 and ICOS, which are responsible for . Production of CTLA4 and ICOS by regulatory T cells decreased as lipid metabolism dropped. "We are just starting to appreciate the importance of lipids in the immune system, particularly in the function of regulatory T cells," Chi said.

Explore further: Modulating the immune system to combat metastatic cancer

Related Stories

Modulating the immune system to combat metastatic cancer

May 24, 2013
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...

Tumor suppressor protein is a key regulator of immune response and balance

July 18, 2011
St. Jude Children's Research Hospital scientists have identified a key immune system regulator, a protein that serves as a gatekeeper in the white blood cells that produce the "troops" to battle specific infections.

Uncleaned cells mean weak muscles

April 23, 2013
The protein complex mTORC1 promotes muscle growth. However, should this complex remain constantly active, it impairs the ability of the cells to self-clean, causing myopathy. Scientists working with Markus Rüegg, Professor ...

Potential new treatment for gastrointestinal cancers discovered

January 17, 2013
(Medical Xpress)—Researchers have identified a complex of proteins that promotes the growth of some types of colon and gastric cancers, and shown that medications that block the function of this complex have the potential ...

Scientists find link between allergic and autoimmune diseases in mouse study

June 4, 2013
(Medical Xpress)—Scientists at the National Institutes of Health, and their colleagues, have discovered that a gene called BACH2 may play a central role in the development of diverse allergic and autoimmune diseases, such ...

Recommended for you

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

First vaccine developed against grass pollen allergy

January 18, 2018
Around 400 million people worldwide suffer in some form or other from a grass pollen allergy (rhinitis), with the usual symptoms of runny nose, cough and severe breathing problems. In collaboration with the Viennese firm ...

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

How the immune system's key organ regenerates itself

January 15, 2018
With advances in cancer immunotherapy splashing across headlines, the immune system's powerful cancer assassins—T cells—have become dinner-table conversation. But hiding in plain sight behind that "T" is the organ from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.