Researchers Find Possible Cellular Mechanism for Autoimmune Disease

Recent research from National Jewish Health has revealed a cellular trigger for autoimmune disease. Autoimmune disease affects between 25-50 million people in the United States, with an interesting gender bias towards women (estimates of around 80% of autoimmune cases are women). The reason for this bias may have to do with an increase humoral immune response, ¹ and this current research may have unpacked further what is driving this autoreactivity of the immune system.

T-bet Deletion Research Results

The research team at National Jewish Health studied Age-associated B Cells (ABCs), and found that there is a transcription factor, T-bet, inside these B cells that cause ABCs to develop and drive autoimmunity.² It has been previously confirmed that ABCs are drivers of autoimmunity³, but not exactly by what mechanism. This research showed that when T-bet was deleted inside B-cells in mice, genetically prone to develop autoimmune disease, the mice remained healthy. The same process is believed to occur in humans.

The ABCs of T-bet Activation

ABCs are a subset of B cells that have in increased responsiveness to TLR7 and TLR9 ligands, and both normal and pathological response.³ Their differentiation is determined seemingly being driven by T-bet to either healthy immune response to viral or bacterial pathogens, or autoimmune disease.² It appears that T-bet is somehow activated inside the cell when a combination of receptors on the B cell’s surface are stimulated (TLR7 and IFN-g).²

Research Reveals

The research study showed that autoimmune-prone mice that were bred without the ability to express T-bet inside B cells remained healthy, and had a 90% survival rate past 12 months – these mice actually did not develop ABCs. The same autoimmune-prone mice with T-bet present, developed autoimmune conditions as expected, as well as 80 percent experiencing kidney damage and 75% dying before 12 months.

Sources

1. Fairweather D, Frisancho-kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. Am J Pathol. 2008;173(3):600-9.
2. K Rubtsova, AV Rubtsov, JM Thurman, et al. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. Journal of Clinical Investigation, 2017; 127 (4): 1392 DOI: 10.1172/JCI91250
3. Naradikian MS, Hao Y, Cancro MP. Age-associated B cells: key mediators of both protective and autoreactive humoral responses. Immunol Rev. 2016;269(1):118-29.

Node Smith, associate editor for NDNR, is a fifth year naturopathic medical student at NUNM, where he has been instrumental in maintaining a firm connection to the philosophy and heritage of naturopathic medicine amongst the next generation of docs. He helped found the first multi-generational experiential retreat, which brings elders, alumni, and students together for a weekend campout where naturopathic medicine and medical philosophy are experienced in nature. Three years ago he helped found the non-profit, Association for Naturopathic ReVitalization (ANR), for which he serves as the board chairman. ANR has a mission to inspire health practitioners to embody the naturopathic principles through experiential education. Node also has a firm belief that the next era of naturopathic medicine will see a resurgence of in-patient facilities which use fasting, earthing, hydrotherapy and homeopathy to bring people back from chronic diseases of modern living; he is involved in numerous conversations and projects to bring about this vision.