Chrysothemis Brown, MBBS, Ph.D.

Research

The Brown lab explores how the immune system learns to tolerate the body’s own tissues as well as harmless foreign proteins such as dietary and microbiota antigens. Loss of tolerance can lead to devastating autoimmune and inflammatory diseases. A window of opportunity exists within the first weeks of life, when the immune system learns how to differentiate between friend and foe. That training begins in the thymus, the gland in which T cells are born and educated by specialized epithelial cells that display an array of self-proteins. But the training does not end there; outside of the thymus the immune system must establish and maintain tolerance to both self-proteins as well as the holobiont self, comprising a complex community of commensal microbes. I have discovered a novel class of antigen-presenting cells that appear to regulate immune tolerance within lymph nodes. Our work so far has established that these cells play a critical role in promoting tolerance to gut microbes. Intriguingly, these cells share features with thymic epithelial cells, suggesting additional roles in tolerance to self. Now, using methods in molecular genetics and immunology, single-cell genomics and computational biology, my lab will assess the role that these cells play in self-tolerance and determine whether they deploy the same mechanisms as antigen-presenting thymic epithelial cells. We will also assess whether these cells can be recruited to foster tolerance in later life. My work could lead to new therapeutic strategies for combatting autoimmune or inflammatory disorders or for enhancing the response to cancer immunotherapies.