James Gardner, M.D., Ph.D.

Research

The Gardner lab is interested in how complex organisms, comprised of diverse tissues and commensal microbial colonies, define immunolologic “self” to maintain tolerance. While adaptive immunity provides powerful abilities to combat an array of ever-evolving pathogens, it comes with substantial risks of autoimmunity and immune dysregulation. We study specific populations of cells that modulate immune responses to help prevent this. One well-known population resides in the thymus and is defined by expression of a gene called the autoimmune regulator (Aire). Early in my career I identified novel populations of Aire-expressing cells that exist outside the thymus, where they appear to play relevant roles in immune homeostasis and tolerance. We termed these populations extrathymic Aire-expressing cells (eTACs) and showed that, for example, they play critical roles in maintaining maternal-fetal tolerance during pregnancy. Recently we and others identified subsets of these cells that may play roles in commensal tolerance in the gut, and also demonstrated that eTACs share a striking transcriptional symmetry with their Aire-expressing counterparts in the thymus despite their distinct lineages. My lab uses advanced methods in bioinformatics, single-cell genomics, and transgenic engineering to define the biology and role of these populations in a range of settings. Our work understanding these fundamental mediators of immune tolerance could lead to novel and transformative approaches for preventing or treating autoimmune disorders, avoiding rejection of transplanted organs, improving tumor immunotherapy, and supporting healthy pregnancy.