Study Identifies Molecular Brake That Controls Overactive Killer T Cells

"Why do immune cells that are expected to destruct viruses abruptly move against our ain body?"

There are instances wherever slayer T cells—which are meant to precisely region virus-infected cells—malfunction for illustration overheated engines, attacking moreover patient cells and damaging tissues. A KAIST investigation squad has now identified nan cardinal system that regulates this excessive activation of slayer T cells, offering caller insights into controlling immune overreactions and processing therapies for immune-related diseases.

KAIST (President Kwang Hyung Lee) announced connected November 5 that a investigation squad led by Professors Eui-Cheol Shin and Su-Hyung Park from nan Graduate School of Medical Science and Engineering, successful collaboration pinch Professor Hyuk Soo Eun from Chungnam National University College of Medicine, has uncovered nan molecular ground of nonspecific activation successful slayer T cells and projected a caller therapeutic strategy to power it.

Killer T cells (CD8⁺ T cells) selectively destruct infected cells to forestall viral spread. However, erstwhile excessively activated, they tin onslaught uninfected cells, causing inflammation and insubstantial damage. Such overactive immune responses tin lead to terrible viral infections and autoimmune diseases.

In 2018, Professor Shin's squad was nan first successful nan world to observe that slayer T cells tin beryllium nonspecifically activated by cytokines and randomly onslaught big cells—a arena they termed "bystander activation of T cells". The existent study builds connected that find by revealing nan molecular system driving this abnormal process.

The squad focused connected a cytokine called interleukin-15 (IL-15). Experiments showed that IL-15 tin abnormally excite slayer T cells by a bystander activation mechanism, causing them to onslaught uninfected big cells. However, erstwhile location is simply a concurrent antigen-specific stimulation, IL-15-induced bystander activation is suppressed.

The researchers further identified that this suppression occurs done an intracellular signaling process. When nan attraction of calcium ions (Ca²⁺) changes, a macromolecule called calcineurin activates, which successful move triggers a regulatory macromolecule known arsenic NFAT, suppressing IL-15-induced bystander activation of slayer T cells. In different words, nan calcineurin-NFAT pathway activated by antigen stimulation acts arsenic a brake connected overactivation by a bystander mechanism.

The squad besides discovered that immoderate immunosuppressants, which are known to artifact nan calcineurin pathway, whitethorn not ever suppress immune responses—in definite contexts, they tin alternatively beforehand IL-15-induced bystander activation of slayer T cells. This uncovering underscores that not each immunosuppressants activity nan aforesaid measurement and that treatments must beryllium cautiously tailored to each patient's immune response.

Through cistron look analysis, nan researchers identified a cistron group that summation only successful abnormally activated slayer T cells induced by IL-15 arsenic markers. They further confirmed that these aforesaid markers were elevated successful bystander slayer T cells from patients pinch acute hepatitis A, suggesting that nan markers could beryllium utilized for illness diagnosis.

This study provides important clues for knowing nan pathogenesis of various immune-related diseases, including terrible viral infections, chronic inflammatory disorders, autoimmune diseases, and organ transplant rejection. It besides paves nan measurement for processing caller immunoregulatory therapies targeting IL-15 signaling.

This study shows that slayer T cells are not simply defenders—they tin toggle shape into 'nonspecific attackers' depending connected nan inflammatory environment. By precisely regulating this abnormal activation, we whitethorn beryllium capable to create caller treatments for intractable immune diseases."

Professor Eui-Cheol Shin

This investigation was published successful nan diary Immunity connected October 31, pinch Dr. Hoyoung Lee and Ph.D. campaigner So-Young Kim arsenic co-first authors.

The study was supported by nan National Research Foundation of Korea (NRF), nan Korea Health Industry Development Institute (KHIDI), and nan Institute for Basic Science (IBS).