Nat Comm . . . The ichitian team proposed a new strategy for treating autoimmune diseases.

Zyme Treg is an essential immunosuppressive cell. Its deficiency leads to autoimmune diseases, called IPEX syndrome, which can be caused by many single gene mutations.IPEX syndrome is currently incurable and usually dies in early infancy or childhood.in many patients, the function of Treg is normal.for such patients, one possible therapy is to use gene editing to repair gene mutations in Treg in situ in patients, so as to restore Treg function, reverse inflammation and treat diseases.this treatment is simple and attractive, but whether it can be achieved is completely unknown.first of all, the vectors carrying gene editor can only infect 7% of T cells when injected into the body, which may not be enough to reverse inflammation.in addition, even if the inflammation can be reversed, it may not be able to save the patient, because when the patient is diagnosed, the disease is usually in a state, the tissue has been damaged, and these fatal injuries may not be able to be repaired.recently, Chi Tian research group of Shanghai University of science and technology published a research paper entitled "in situ conversion of defective Treg into supertreg cells to treat advanced IPEX like disorders in mice" in nature communications, and proposed a new therapy to treat IPEX like disorders by in situ transformation of defective regulatory T cells into supertreg.previously, the research group found that knockout of BRG1 in mouse Treg can induce fatal autoimmune diseases similar to IPEX.in this project, the researchers used the self-developed reversible knockout technology to restore the expression of BRG1 in the dying mice with BRG1 knockout.the results were unexpected: if BRG1 expression was restored in a small fraction (minimum 8%) of Tregs, it was sometimes enough to save mice.the reason is that after the expression of BRG1 is restored, Treg is rapidly activated and transformed into a powerful supertreg under the strong stimulation of a large number of proinflammatory factors in the environment. The latter immediately migrates to the inflammatory tissue and kills the pro-inflammatory immune cells, thus reversing the inflammation. The damaged tissue has a strong repair ability (which may benefit from the tissue repair function of supertreg) The mice recovered to health.it is important that as the inflammation subsides, supertreg gradually loses its super function, thus preventing excessive immunosuppression and its serious side effects.This study suggests a simple, effective and safe new therapy for some patients with IPEX syndrome: as long as gene editing technology is used to correct gene mutations in a few Tregs in the body of patients, it is possible to use the strong inflammatory environment in vivo to transform these Tregs into supertregs and achieve obvious curative effect.supertreg mechanism model in this paper, Li Yongqin, Chen Yuxin and Mao Shaoshuai, three doctoral students in the school of life, sun Jianlong and Wang fupeng participated in the work, Professor Chi Tian was the corresponding author, and Shanghai University of science and technology was the first completion unit.original link: plate maker: old wings