Nat Immunol: Discover the key molecules that control the production of antibodies!

, June 30, 2020 /
Scientists at the BiovalleyBIOON/LJI have found a new possible new way to better fight a range of infectious diseases, cancer and evenautoimmunediseasesa new study recently published in the journal NatureImmuno
logy shows how a protein acts as a "master regulator" in the immune systemThe study is an important step in developing vaccines and therapies that can "activate" immune cells to help produce anti-disease antibodiesScientists may also "turn off" these cells to combat immune cell dysfunction inautoimmunediseases"
This type of cell (Tfh cells) sometimes has adverse effects onautoimmunediseases -- especially autoantibody diseases such as lupus,rheumatoid arthritisand dry syndrome," said DrShane Crotty, a lJI researcher who led the new study"So hopefully, our basic knowledge of this cell circuit will help us understand how to shut it down in autoimmune diseases."Photo Credit: Jinyong Choi, La Jolla Institute forCrotty's lab is studying key immune system participants, such as different types of auxiliary T-cellsIn 2009, his lab published a study showing that a protein called Bcl6 controls the differentiation of auxiliary T cells in the body to do different thingsThey found that Bcl6 causes auxiliary T cells to become T-foam-assisted T cells (Tfh), which together with B cells produce powerful antibodiesthis is an important breakthrough, but Crotty's lab still wants to know: What exactly does Bcl6 do to Tfh cells? Answering this question can open the door to controlling the immune response"There is a lot of interest in using Tfh cell-related biologically enhanced vaccines," saidCrottyResearchers are also interested in Tfh cell-related biology in human autoimmune diseases, allergies, atherosclerosis,organ transplantsand cancer treatment interventions"
in this new study, Crotty leads a complex effort to test how Bcl6 controls Tfh's theory of competitionThe researchers used mouse models and a series of gene sequencing tools to determine that Tfh cells actually needed Bcl6 to exist on closer inspection, the researchers found that Bcl6 is primarily a inhibitor of auxiliary T cells, which means that it blocks the expression of other proteins in these cells through a series of gene switches, and they map these gene switches these new maps show that Bcl6 controls a "double negative circuit" "The Bcl6 protein turns on this cell type, but we know it only shuts down this type of cell," Crotty explains So we did a lot of experiments to figure out how it controls cells through a series of double-inhibition signals It shuts down genes that shut down other genes "
Bcl6 blocks the expression of two proteins that usually prevent Tfh cell differentiation When Bcl6 comes into play, auxiliary T cells are free to become Tfh cells when the body needs them Crotty says the new study provides scientists with a guide on how to control the immune response by turning Bcl6 on or off "There is certainly a growing focus on how to apply this knowledge to Tfp-related treatments." Picture Source: Nature
the body also uses the genetic circuitcontrolled by Bcl6 to stay healthy without the ability to create antibodies that mistakenly attack its own cells "The system needs to correct itself and prevent attacks If an immune response is needed to fight pathogens, the body needs to adjust itself and return to a stable state But Bcl6-Tfh system defects can lead to autoimmune or immunodeficiency The new study suggests that adjusting the immune response through Bcl6 also helps control autoimmune diseases such as multiple sclerosis and type 1 diabetes through Bcl6, Tfh could theoretically be used to treat allergies, reject organs from transplanted organs and help prevent atherosclerosis "Heart disease is now considered to have a large immune factor, as is too much inflammation," Crotty said Better cancer treatment could also include adjusting Tfh to reduce unnecessary immune responses, he added Crotty added that the way Bcl6 controls the expression of the positive Tfh gene may represent a model for studying other puzzling biological switches "We have to do a lot of genetic to connect these points, but this double negative circuit may actually be the way many immune system cells are controlled, " he said " (biovalleybioon.com) reference: Scientists sifae a powerful protein behind antibody development Bcl-6 is the nexus srillion factor of the tll helper sgus via repressor-fe-repressor circuits
, Nature Logic (2020) DOI: 10.1038/s41590-020-0706-5
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