Researchers find promising new approach to stop intestinal problems caused by immune cells

Bolstering a specific enzyme within the mitochondria of intestinal cells helped mitigate GI disease induced by T cells after bone marrow transplant, cancer immunotherapy.

10:19 AM

Author | Nicole Fawcett

microscopic colorful rainbow cells black background and yellow badge on bottom right and blue lettering saying lab notes
Images provided by Pavan Reddy, M.D.

When they are not fighting off diseases and infections, immune T cells can sometimes turn on the gastrointestinal system, causing problems such as autoimmune inflammatory bowel disease, graft-vs.-host disease from a bone marrow transplant or colitis from cancer immune checkpoint blocker therapies.

While traditional treatments for these conditions have focused on manipulating the immune system to mitigate these diseases, researchers at the University of Michigan Health Rogel Cancer Center took an entirely new approach.

"We asked whether there is anything intrinsic to the target intestinal cells themselves that gives them a greater ability to tolerate an attack from the immune cell," said Pavan Reddy, M.D., division chief of hematology/oncology and deputy director at the Rogel Cancer Center.

The team discovered a metabolic alteration within the intestinal epithelial cells that happens exclusively in these T cell-mediated gastrointestinal diseases. A series of experiments in seven different mouse models found that when an enzyme called SDHA is reduced, GVHD, IBD and immune checkpoint-related colitis got worse. SDHA levels were impacted only in the GI system and not in other organs.

The researchers also looked at several potential options to restore SDHA, including the metabolite butyrate, which Reddy's lab had previously identified as playing a role in the gut microbiome. More research is needed to understand how best to increase the level of SDHA, but it provides a promising target.

"Focusing on the target instead of the immune cells is an additional way to mitigate immune-mediated disease. This may take us away from suppressing the immune system, which often leads to infection," said study co-first author Keisuke Seike, Ph.D., a postdoctoral fellow in Reddy's lab.

Funding for this work was from National Institutes of Health grants HL090775, CA173878, CA203542, HL149633, K08HL130944, DK081943, DK89503 and CA46592; Japan Society for the Promotion of Science; the YASUDA Medical Foundation; the Kawasaki Foundation of Medical Science and Medical Welfare; the Ryobiteien Memorial Foundation; the MSD Life Science Foundation Public Interest Incorporated Foundation, the Okayama Medical Foundation, the SENSHIN Medical Research Foundation, the Kato Memorial Bioscience Foundation; and the NOVARTIS Foundation.

Paper cited: "Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology," Nature Immunology, DOI: 10.1038/s41590-021-01048-3

More Articles About: Lab Notes Cancer: Cancer Types Bone and Marrow Transplant (BMT) Cancer Research Rogel Cancer Center Cancer: Help, Diagnosis & Treatment Bone Marrow Transplant (BMT)
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of healthcare news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]


Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Featured News & Stories DNA helix technology robotic cybernetic image
Health Lab
Metabolite tells cells whether to repair DNA
Findings from researchers at the University of Michigan Health Rogel Cancer Center, published in Cancer Discovery, show how a specific nucleotide metabolite called GTP controls responses to radiation and chemotherapy in an unexpected way.
Doctors with patient while on exam table
Health Lab
Can personalized care prevent overscreening for colorectal cancer in older adults?
Study reveals presenting adults between 76 and 85 with personalized information about the benefits and harms of colon cancer screening decreases excess screening
cancer cell yellow blue
Health Lab
Potato starch supplements could be solution to bone marrow transplant complications
University of Michigan Health Rogel Cancer Center scientists have found a potential solution for preventing a common and dangerous complication in patients that receive stem cell transplants from a donor’s blood or bone marrow.  
older person pouring pills into hand close up
Health Lab
Early findings suggest this cancer drug may be effective against advanced tumors caused by genetic mutations
Sparrow Health System, part of University of Michigan Health, experts release findings in a study of a cancer drug for patients with genetic mutations.
Health Lab
Tumor-destroying soundwaves receive FDA approval for liver treatment in humans
Michigan Medicine has developed a new technique that provides a non-invasive alternative to surgery, chemotherapy and radiation treatments for cancer.
Health Lab
Hungry for more
Metabolism pathways make tumors sensitive or resistant to treatments. A collaborative group leverages these avenues to explore the growing foundation of new potential therapies