Littman’s laboratory studies the molecular mechanisms involved in the specification of distinct T lymphocyte lineages during development in the thymus and in response to microbial challenges in peripheral tissues. Elucidation of these mechanisms will help scientists understand how normal protective immune responses differ from pathogenic ones that result in inflammation and autoimmune disease. A major goal is to determine how intestinal commensal bacteria can trigger systemic T cell-mediated autoimmune diseases, and Littman and his team are investigating the roles of diverse myeloid cell types, innate lymphoid cells, enteric neurons, and cytokines in the differentiation of the multiple types of T cells.
2023 Innovation Fund:
As an Innovation Fund investigator, Dan Littman, M.D., Ph.D., is teaming up with Michael Birnbaum, Ph.D., to study the pathology of inflammatory bowel disease (IBD), an autoimmune disorder whose cause is largely unknown. Our intestines host hundreds of species of bacteria that provide mutual benefit to the host by instructing immune system development. However, in individuals with IBD, bacteria that should be harmless, or even helpful, cause an inflammatory T cell response. This collaboration will combine Littman’s research in how specific bacteria drive inflammation by affecting T cell differentiation with Birnbaum’s expertise in T cell receptor-antigen binding to characterize which microbes and antigens drive harmful responses in the gut. The findings from this work have the potential to uncover novel therapies for IBD by targeting either microbes or T cells.
2017 Innovation Fund:
As an Innovation Fund investigator in 2017, Littman teamed up with Robert C. Froemke, Ph.D., to explore new topics at the interface between neuroscience and immunology and used techniques from one system to investigate the other. The pair used novel tools to probe how the neuronal sensing of gut microbes and intestinal functions alters an animal’s behavior—work that could help map how information is relayed from the gut to the nervous system to promote recovery from an illness.