Assistant professor Washington University School in St. Louis saint louis, Missouri, United States
Abstract Text: Dendritic cells (DCs) are key antigen-presenting cells that control both immunity and tolerance. Understanding the principles by which DC control these responses have provided a rich basis for studying and improving clinical outcome in treating human diseases. Part of the complexity is due to the existence of distinct DC subsets, each bearing different microbial receptors, surface molecules and cytokine expression. The biological raison d’être for separate DC subsets has been the focus of many studies, including our own. Our research focuses on skin-migrated DC2 lineage cells, specifically on two subtypes differentiated by CD5 expression. The CD5+ DCs are highly efficient at priming cytotoxic CD8+ T cells and induce inflammatory T helper cell responses compared to their CD5- counterparts. Their elevated levels in inflamed psoriatic skin plaques, where high effector T cell responses are seen, compared to distal cutaneous tissue, suggest they are critical players in the pathogenesis. On the other hand, CD5+ DC numbers are reduced in malignant tissues and correlate with cancer patient survival. Consistent with this notion, we demonstrate, using human patient cells and mouse models, that CD5 functions to trigger an inflammatory pathway of DC maturation and effector T cell activation. Deletion of CD5 on DCs educes tumor rejection and immunotherapy response. During successful immunotherapy, CD5+ DCs increased, which was critical for their interaction with CD5hi T cells. Thus, understanding the function and development of CD5-expressing DCs in immune regulation provides insight into how ICB immunotherapies work and identifies CD5 on DCs as a potential therapeutic target.
