Changchun Xiao, PhD

Scripps Research Institute, La Jolla, CA

2009 B Cells

Functional Analysis of MicroRNAs in Systemic Immune Tolerance

The immune system uses a mechanism called “tolerance” to avoid attacking its own tissues and organs while still being able to respond to infection by foreign substances. When "tolerance" breaks down, lupus and other autoimmune disease can arise.

With the 2009 Novel Research Grant, Dr. Xiao set out to analyze genes that appear to play an important role in orchestrating this system of immune tolerance, focusing specifically on a newly discovered class of regulators of gene expression—microRNAs. Led by Dr. Xiao, the team identified a family of molecules called microRNAs that regulate immune responses. Mice that lack these molecules lose their normal infection-fighting ability while those mice that produce too many develop a fatal autoimmune syndrome.

“This finding gives us insights into immune regulation that could be very helpful in a range of medical applications, from viral vaccines to treatments for autoimmune diseases,” commented Dr. Xiao. The paper appears online in the June 30, 2013 issue of Nature Immunology.

Unraveling a Crucial Process

The finding identifies a key role for microRNAs in controlling the interaction between T cells and B cells, the armies that make up most of the immune system. B cells, which produce antibodies, usually lie in wait for a virus or bacteria but need to be physically activated by T cells to start producing antibodies to fight them off.

Xiao and his colleagues plan to investigate methods to harness the microRNAs to boost antibody responses – to vaccines for example— as well as to lower production of autoantibodies in people with autoimmune diseases such as lupus.

In addition to producing key findings on B-cell tolerance specifically, Dr. Xiao’s innovative work will shine new light on how “tolerance” works in lupus and autoimmunity.

Select Publications:

MicroRNAs of the miR-17~92 family are critical regulators of TFH differentiation. Seung Goo Kang,1, 5 Wen-Hsien Liu,1, 5 Peiwen Lu,2, 5 Hyun Yong Jin,1, 3 Hyung W Lim,4 Jovan Shepherd,1 Daniel Fremgen,1 Eric Verdin,4 Michael B A Oldstone,1 Hai Qi,2 John R Teijaro1 & Changchun Xiao1 Journal name:Nature Immunology.Volume:14. Pages:849–857Year published: (2013)