The Campbell laboratory is interested in understanding the basis for T cell activation, function and tolerance. We use both animal models and human samples to identify functionally relevant populations of effector and regulatory T cells, define the factors that promote their development and maintenance, and delineate their roles in healthy immune responses, and in immune-mediated diseases such as multiple sclerosis, type 1 diabetes, allergic diseases and scleroderma. The Lab is also interested in determining how the T cells interact with epithelial cells in tissues such as the skin and lungs to regulate normal tissue function, and understanding how this changes during disease.
A full list of Campbell Lab publications can be found at NCBI.
Molecular control of regulatory T cells
Regulatory T cells (Treg cells) that express the transcription factor Foxp3 have a key role in maintaining normal immune function and preventing autoimmune disease. In published studies, the Campbell Lab has determined that Treg cells are specialized to migrate to and function within specific tissue sites such as the skin, intestines or adipose tissue. Furthermore, the lab has shown that inflammatory signals can influence the migration and function of Treg cells. The lab is working to further understand the molecular basis for this specialization and identify the relevant signals that control their migration and function in different immune environments.
The incidence of autoimmunity is rapidly growing in the developed world, indicating that environmental inputs have a strong effect on loss of self-tolerance and development of autoimmune disease. Thus, the Campbell Lab is examining how factors such as diet, prior infection history and microbiome shape the abundance and function of Treg cells in different tissue sites, and how this in turn impacts tolerance induction, development of autoimmune disease and responses to immune-modulating therapy.
Novel signaling pathways that control effector T cells
Upon activation, effector T cells integrate signals from the T cell receptor, co-stimulatory receptors and immunomodulatory cytokines to drive their clonal expansion and their differentiation into specialized effector and memory T cell populations. The Cambpell Lab recently demonstrated that in CD8+ T cells, the signaling adaptor BCAP is a key regulator of these processes, and that loss of BCAP mediated signaling impairs the clonal expansion of antigen-specific CD8+ T cells, and their subsequent differentiation into long-lived memory cells. Ongoing work in this area is focused on further defining BCAP-dependent signals in activated T cells, and understanding the transcriptional basis by which they control effector and memory T cell function.
Regulation of Cutaneous Immunity and Tissue-Repair
The Campbell Lab has recently identified a novel population of CD4+ T cells in human blood that phenotypically, functionally and transcriptionally resemble skin resident T cells that may help control wound-healing responses following tissue damage.Current studies in the lab are focusing on identifying the signals that control the differentiation and function of these T cells, and understanding how they influence the behavior of other skin-resident cell populations such as keratinocytes and fibroblasts and macrophages to coordinate host-protective and tissue-repair responses following infection or trauma.