In a study published today in Cell, scientists created the first retroviral CRISPR–Cas9 gene editing library to explore the regulation of mouse T cells. The research team mapped the most important genes for controlling T helper cells and identified several new regulatory genes. This knowledge could help scientists that are looking to develop new treatments to prevent autoimmunity or to activate the immune system against infection or tumor cells.
It is vital that the activation and differentiation of T helper cells is well controlled. Ineffective T helper cells leave an infection unchecked, whereas if they are too active, the body can attack itself. However, it is unclear exactly what signals activate these cells, tell them how to differentiate, or specify which chemical signals they release.
To investigate these questions, the researchers created a new genome-wide CRISPR library of 88,000 guides that enabled them to switch off each of the 20,000 genes from mouse T helper type 2 (Th2) cells. After mimicking an infection in cultured Th2 cells, they studied how switching off each single gene in the genome affected activation and differentiation. They found many different genes that are involved in regulating Th2 development and were able to define the gene regulatory network.
“This study will help drive forward our understanding of the immune system,” says senior author Dr. Sarah Teichmann from the Wellcome Sanger Institute and University of Cambridge. “We have created an atlas of the most important genes involved in the regulation of T helper cell immune response, and highlighted particular genes for further study. This openly available resource will be extremely useful for scientists studying the immune system, and could lead to finding new immune-activating therapeutics against tumours and infections, or for damping down the immune response to relieve allergies in the future.”