By Ali Pattillo ∙ Aug 1, 2020
When the immune system is battling an invader like cancer or a virus over long stretches of time, it can get tired. In a recent study, researchers discovered what could help stave off this “immune exhaustion.”
According to research conducted in mice, skeletal muscle can keep the immune system from running out of steam when fighting chronic illnesses. That’s because muscles can shelter certain types of T-cells and replenish immune system ranks when they become fatigued.
Jingxia Wu is the study’s first author and a researcher at the German Cancer Research Center. She explains that this sheltering helps the immune system when it’s been continuously fighting a virus over a long period of time.
“If the T-cells, which actively fight the infection, lose their full functionality through continuous stimulation, the precursor cells can migrate from the muscles and develop into functional T-cells,” Wu says.
If the findings are found in humans, not just mice, that could mean weightlifting and building muscle keeps people’s immune system awake, alive, and alert too.
The study was published June 12 in the journal Science Advances.
The link between muscles and immunity — When people become sick with chronic viral infections or cancers, they often lose weight and muscle mass, experiencing a medical phenomenon known as cachexia.
Meanwhile, these populations can also lose T-cells, one of the major players involved in the adaptive immune system. T-cells also become fatigued when fighting these bodily invaders over time.
Until now, researchers haven’t fully understood if and how these separate phenomena — muscle mass and T-cell exhaustion — were linked.
“It is known that T-cells are involved in the loss of skeletal muscle mass,” co-author Guoliang Cui explains. “But whether and how, in turn, skeletal muscles influence the function of the T-cells is still unclear.”
To answer this puzzling question, scientists rounded up a group of mice and infected them with lymphocytic choriomeningitis virus (LCMV). This model is commonly used to study acute and chronic infections in mice.
The researchers then analyzed the gene expression in the skeletal muscles of the mice. They found that during chronic infections, the mice’s muscle cells release an increased amount of interleukin-15. This cytokine signals a group of T-cells (called CD8+) to settle in the skeletal muscles.
Hidden away, these T-cells are sheltered from chronic inflammation throughout the body. Then, when other T-cells become exhausted, these muscle T-cell pockets replenish T-cell pools. This helps the mice sustain better long-term antiviral immunity.
Ultimately, the researchers write, this study reveals a “mechanistic link between these two seemingly isolated events” — T-cell exhaustion and muscle mass.
In a global pandemic that makes immune system function more crucial than ever, these findings hint at a possible way to keep immunity strong: weightlifting.
However, since these findings weren’t conducted in people, we don’t know whether muscles play the same cheerleader role to the human immune system.
Even though we’re waiting for human experiments to confirm the findings, it is still worth picking up a kettlebell. Strength training has a long list of benefits — on top of potentially boosting the immune system. It strengthens the nervous system, prevents bone loss, and increases flexibility as people age.
LONGEVITY HACKS is a regular series from Inverse on the science-backed strategies to live better, healthier, and longer without medicine.
HOW THIS AFFECTS LONGEVITY — Researchers discover that skeletal muscle can replenish T-cell pools and keep the immune system from becoming exhausted. At least in mice.
WHY IT’S A HACK — Unlike a lot of the immune “boosters” sold online, exercise works — when it comes to supporting optimal immune function.
SCIENCE IN ACTION — The study suggests on top of promoting a healthier brain and bones, strength training keeps the immune system from becoming exhausted. Burn baby, burn.
HACK SCORE OUT OF 10 — 🏋🏽♀️🏋🏽♀️🏋🏽♀️🏋🏽♀️🏋🏽♀️🏋🏽♀️(6/10 squat presses)
Abstract: CD8+ T cells become functionally impaired or “exhausted” in chronic infections, accompanied by unwanted body weight reduction and muscle mass loss. Whether muscle regulates T cell exhaustion remains incompletely understood. We report that mouse skeletal muscle increased interleukin (IL)–15 production during LCMV clone 13 chronic infection. Muscle-specific ablation of Il15 enhanced the CD8+ T cell exhaustion phenotype. Muscle-derived IL-15 was required to maintain a population of CD8+CD103+ muscle-infiltrating lymphocytes (MILs). MILs resided in a less inflamed microenvironment, expressed more T cell factor 1 (Tcf1), and had higher proliferative potential than splenic T cells. MILs differentiated into functional effector T cells after reentering lymphoid tissues. Increasing muscle mass via muscle-specific inhibition of TGFβ signaling enhanced IL-15 production and antiviral CD8+ T cell responses. We conclude that skeletal muscle antagonizes T cell exhaustion by protecting T cell proliferative potential from inflammation and replenishing the effector T cell progeny pool in lymphoid organs.
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