Preventing too much immunity - Medical Xpress
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Preventing too much immunity 27 December 2016 Credit: Osaka University Scientists at the Immunology Frontier Research Center (IFReC), Osaka University, Japan, report a new molecular mechanism that could explain the cause of some autoimmune diseases. While the immune system is crucial for protecting the body from infection and disease, prolonged activation can damage healthy tissue. After its activation, the immune system is shut off by specialized immune cells known as regulatory T cells (Treg cells). Understanding the development of Treg cells is thought to be critical for combating autoimmune diseases . "The development of Treg cells in the thymus depends on super-enhancer establishment," explains IFReC Professor Shimon Sakaguchi. This super-enhancer establishment permits the expression of genes specific for Treg cell development . "Super-enhancers appeared to be a pre-requisite for Treg cell development, so we sought molecules controlling super-enhancers," he added. In the most recent publication by the Sakaguchi lab, which can be seen in Nature Immunology, Sakaguchi and his team report that Satb1 regulates the super enhancers essential for Treg cell development. Looking at the Treg cell development pathway, the scientists found that the level of Satb1 was highest before Treg cells develop, and dropped after Treg cell development. Further study showed that Satb1 bound to the super enhancers responsible for Treg cell development, but again, only in progenitors that differentiated into Treg cells and not Treg cells themselves. Therefore, Satb1 may regulate the epigenetic changes that precede the creation of Treg cells. "Satb1 appears to be necessary for the differentiation of Treg cells, but not for the maintenance of Treg cells," said Dr. Yohko Kitagawa, who first-authored the study. Indeed, in mice lacking Satb1, the development of Treg cells was impaired and the mice showed symptoms of autoimmune disease. Furthermore, the progenitors cells of these mice showed inferior super enhancer activity, which resulted in less expression of the genes necessary for Treg cell development. Based on these findings, Sakaguchi theorizes that defective Satb1-dependent super-enhancer establishment could be a cause of autoimmune diseases and allergy. "Autoimmune diseases are 1 / 2
Transcript of Preventing too much immunity - Medical Xpress
Preventing too much immunity27 December 2016
Credit: Osaka University
Scientists at the Immunology Frontier ResearchCenter (IFReC), Osaka University, Japan, report anew molecular mechanism that could explain thecause of some autoimmune diseases.
While the immune system is crucial for protectingthe body from infection and disease, prolongedactivation can damage healthy tissue. After itsactivation, the immune system is shut off byspecialized immune cells known as regulatory Tcells (Treg cells). Understanding the developmentof Treg cells is thought to be critical for combating
autoimmune diseases. "The development of Tregcells in the thymus depends on super-enhancerestablishment," explains IFReC Professor ShimonSakaguchi.
This super-enhancer establishment permits theexpression of genes specific for Treg celldevelopment. "Super-enhancers appeared to be apre-requisite for Treg cell development, so wesought molecules controlling super-enhancers," headded.
In the most recent publication by the Sakaguchi lab,which can be seen in Nature Immunology,Sakaguchi and his team report that Satb1 regulatesthe super enhancers essential for Treg celldevelopment.
Looking at the Treg cell development pathway, thescientists found that the level of Satb1 was highestbefore Treg cells develop, and dropped after Tregcell development. Further study showed that Satb1bound to the super enhancers responsible for Tregcell development, but again, only in progenitors thatdifferentiated into Treg cells and not Treg cellsthemselves. Therefore, Satb1 may regulate theepigenetic changes that precede the creation ofTreg cells.
"Satb1 appears to be necessary for thedifferentiation of Treg cells, but not for themaintenance of Treg cells," said Dr. YohkoKitagawa, who first-authored the study.
Indeed, in mice lacking Satb1, the development ofTreg cells was impaired and the mice showedsymptoms of autoimmune disease. Furthermore,the progenitors cells of these mice showed inferiorsuper enhancer activity, which resulted in lessexpression of the genes necessary for Treg celldevelopment.
Based on these findings, Sakaguchi theorizes thatdefective Satb1-dependent super-enhancerestablishment could be a cause of autoimmunediseases and allergy. "Autoimmune diseases are
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due to hyperactive immune systems. One cause isnot having enough Treg cells. Understanding howthis occurs is an important step towards treatingautoimmune diseases," he said.
More information: Yohko Kitagawa et al.Guidance of regulatory T cell development bySatb1-dependent super-enhancer establishment, Nature Immunology (2016). DOI: 10.1038/ni.3646
Provided by Osaka UniversityAPA citation: Preventing too much immunity (2016, December 27) retrieved 17 March 2022 from https://medicalxpress.com/news/2016-12-immunity.html
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