Finnish Researchers Uncover Immune Mechanisms in an Autoimmune Disorder, Offering Hope for Potential Treatments
An international study led by researchers from the University of Helsinki highlights the role of natural killer cells in aplastic anemia, a life-threatening autoimmune disease. Targeting NK cells and NK-like T cells holds therapeutic potential in aplastic anemia and possibly in other autoimmune disorders.
Almost 10% of the Western population is affected by various autoimmune diseases. Aplastic anemia is a rapidly developing, life-threatening autoimmune disorder where the body’s immune system destroys the blood-forming cells in the bone marrow. Conventionally, main focus of aplastic anemia studies has been on T cells, which existing available therapies aim to suppress. Treatments are untargeted, predisposing patients to side-effects and serious infections. Although current therapies can cure a majority of the patients, a significant proportion, almost one-third do not get a response to immunosuppressive treatment or succumb to the disease.
“If we can effectively suppress the T cells but see that the clinical disease persists, should we look also besides the T cells? Which are the T cells attacking stem cells in the first place and can that information help us getting better treatment options for these patients?” asked Jani Huuhtanen, physician scientist specializing in hematology and one of the lead-authors of the study.
These questions prompted an international team of researchers to study the entire immune system with an unbiased approach by utilizing cutting-edge single-cell analysis techniques. Surprisingly, the researchers discovered that a subset of patients had more NK cells than cytotoxic T cells at the disease site the bone marrow. To validate their results, they compared the results to a larger cohort from the US, showing the same result.
“The rarity of aplastic anemia made gathering patient samples from Finland, Sweden, the US, and Australia especially important to confirm our observation and broaden the study’s impact”, tells Satu Mustjoki, professor of translational hematology and the head of Translational Immunology research Programme.
Although the NK cells looked like highly active killers, in a series of experiments the researchers identified that NK cells cannot kill the blood-forming cells on their own, but appear to support T cells in autoimmunity. This synergy could be also seen in T cells, as T cells acquired key characteristics of NK cells. These ”NK-like” T cells carried T cell receptors with specific sequence fingerprints, leading researchers to believe that these T cells could recognize the same target in stem cells, triggering the disease.
The identification of NK cells and NK-like T cells as central to aplastic anemia holds great potential for developing more effective treatments for the condition and, possibly, for other autoimmune diseases as well. T cell receptor fingerprints could direct researchers to discovery of public antigen targets in AA, leading to more targeted therapies for patients.
“Our research not only highlights the importance of NK and NK-like T cells in aplastic anemia but also raises the potential for exploring these cells in other autoimmune diseases”, explains Sofie Lundgren, physician-scientist and one of the lead-authors of the study. “We are now investigating their role in other autoimmune disorders, such as type 1 diabetes, inflammatory bowel disease, and multiple sclerosis”.
This study, published in Science Translational Medicine, holds promise for more effective, targeted treatments for aplastic anemia, and possibly for other autoimmune disorders.
Lue tiedote tutkimuksesta suomeksi Helsingin yliopiston sivuilta.
More information:
Jani Huuhtanen, MD, PhD, University of Helsinki and Aalto University
Phone: +358 50 4350 191, email: jani.huuhtanen@ican-core
Sofie Lundgren, MD, PhD, University of Helsinki
Email: sofie.lundgren@helsinki
Prof. Satu Mustjoki, Translational Immunology Research Program, University of Helsinki
Email: satu.mustjoki@helsinki.fi, phone: +358 9 471 71898
Sofie Lundgren and Jani Huuhtanen et al. Single-cell analysis of aplastic anemia reveals a convergence of NK and NK-like CD8+ T cells with a disease-associated TCR signature. Sci. Transl. Med. 17, eadl6758(2025). DOI:10.1126/scitranslmed.adl6758