UTSW Research: RNA Exosome Keys for B Cell Development: Newsroom

Dr. Nanyang

Dallas – June 13, 2022 – UT Southwestern new research shows that RNA exosomes (cell machines that break down old RNA molecules) play an important role in B cell development, protecting the immune system from infection. Essential to your ability. ..Survey results published in Scientific immunologyExplain why patients with rare mutations in the gene encoding this mechanism are often immunocompromised and can offer new approaches to treat autoimmune diseases.

“It was very surprising to us that we realized that this gene, whose role is well known as part of the RNA disposal system, is also important for a very important part of the immune system.” Said the research leader. Dr. Nanyang,Professor Immunology When Microbiology As a member with UT Southwestern Harold C. Simmons Comprehensive Cancer Center..

Many patients with a rare disease associated with RNA exosome deficiency known as capillary bowel syndrome (THES) also develop B-cell immunodeficiency and experience recurrent infections.Researchers have long known that THES is associated with mutations in genes encoding exosomes known as: SKIV2L When TTC37The molecular basis of the disease was unknown.

Christian Wisokki, MD, Ph.D.

To better understand the role of SKIV2L At THES, Dr. Yan’s research team at the Faculty of Immunology and colleagues at UTSW’s Primary Immunodeficiency Clinic and Dallas Pediatric Medical Center have studied THES patients with this variant. Christian Wisokki, MD, Ph.D., Associate Professor of Pediatrics. In addition to the usual clinical features of THES, small size at birth, refractory diarrhea, unique “Woolly” hair, and multi-organ disorders with symptoms such as liver disease, this patient has a very high B cell blood cell count. It was few.

Then the researchers generated that mouse SKIV2L The gene was deleted in the bone marrow stem cells that produce B cells. Animals also had B cell defects. Further studies show that B cells did not mature because they did not develop a significant part of their development, where progenitor cells randomly recombined genetic material to create a diverse pool of B cells. I did.

Hematoxylin and eosin staining Skiv2l-Defective mouse lymph nodes. Normal lymph nodes should have large, organized B-cell follicles along the cortex (outer edge).The Skiv2l-Defective lymph nodes have no B cells and no organized B cell follicles.

Dr. Yang explained that this seems to be related to SKIV2LRole in RNA degradation.Another survey result published in the same issue of Scientific immunology, Researchers at Columbia University have shown that mutations in other components of RNA exosomes also cause B cell deficiency. These mutations cause RNA exosomes to fail and cells selectively retain non-coding forms that do not produce RNA, especially proteins. When B cell progenitor cells become cancerous with excess non-coding RNA, they cannot mature into functional B cells.

Taken together, the findings suggest that THES may be treated with bone marrow transplants to replace defective B-cell progenitor cells with genetic mutations with healthy ones.they again SKIV2L Overactive B cells may provide new targets for combating autoimmune diseases such as lupus, which play an important role. Dr. Yang explained that by inhibiting the activity of this gene, it may be possible to control the number of B cells and reduce the intensity of autoimmune attacks.

Dr. Yang is a scholar of Rita C. and William P. Clements Junior Medical Research.

Other UTSW researchers who have contributed to this study include Kun Yang (lead author), Jie Han, Jennifer G. Gill, Jason Y. Park, Meghana N. Sathe, Jyothsna Gattineni, and Tracey Wright. M. Teresa de la Morena of the University of Washington also contributed.

This study was supported by grants from the National Institutes of Health (AI153576) and the Burrows Welcome Foundation.

About UT Southwestern Medical Center

UT Southwestern is one of the leading academic medical centers in the United States, integrating pioneering biomedical research with outstanding clinical care and education. The institution’s faculty has won six Nobel Prizes and includes 26 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 researchers at the Howard Hughes Medical Institute. Over 2,900 full-time faculty members are responsible for breakthrough medical advances and are committed to rapidly transforming science-led research into new clinical therapies. UT Southwestern physicians provide care in more than 80 disciplines and oversee nearly 4 million outpatients annually for more than 100,000 inpatients and more than 360,000 emergency room cases. increase.