The immune system is a complex cellular network that needs to be tightly coordinated and appropriately regulated to protect against pathogens, autoimmune disease and cancer. This system is broadly divided into adaptive and innate components; adaptive immune cells include B and T lymphoid cells, express antigen-specific surface receptors and are maintained in a naïve effector state that must be activated following pathogen encounter, thus leading to slow immune responses. Immediate control of a pathogenic infection requires the function of innate immune cells that belong to the myeloid lineage and rely on germline-encoded receptors to provide a fast, albeit largely non-pathogen specific, response. In addition, there are certain cell types of the lymphoid lineage that exhibit characteristics of innate cells, collectively known as innate lymphocytes, including (but not limited to), Natural Killer T (NKT) cells and the recently identified Innate Lymphoid Cells (ILCs). Functionally, both ILCs and NKT cells acquire effector properties that closely resemble those of the adaptive CD4+ T helper (Th) cell programs, in terms of cytokine and transcription factor profiles. Developmentally, adaptive lymphocytes acquire their effector programs only after antigen and cytokine co-stimulation, during an immune response. In contrast, innate lymphocyte effector programs are “hard-wired” during development prior to foreign antigen exposure, are maintained throughout life and are largely independent of tissue residency. Our research aims at understanding the mechanisms that determine the cell fate of innate T lymphocytes during development.
Our research explores the central hypothesis that cell fate is determined by unique gene expression programs that direct the developmental pathway of progenitors, as well as the maintenance, homeostasis and function of mature cells and at the same time repress alternative lineage choices. This process is largely instructed by transcriptional regulatory networks that can integrate microenvironmental signals and directly regulate gene expression. The stability or plasticity of a specific cell identity is ultimately linked to the epigenetic control of chromatin organization that regulates proper transcription factor accessibility in time and space. Our laboratory is interested in understanding the transcriptional networks and chromatin dynamics that control cell fate decisions and contribute to the initiation and establishment of the innate lymphocyte programs and how alterations in these pathways may lead to disease.