Wednesday, January 15, 2025
1/15/2025
PROJECT SUMMARY/ABSTRACT This proposal is a supplement to R01 AI156534, “The role of IL-37 in human regulatory T cells,” designed to enhance the training of Dr. Cameron Lloyd, PhD, who will be hired as a postdoctoral fellow in the Department of Dermatology at the University of Colorado, Anschutz Medical Campus. Understanding peripheral tolerance and the maintenance of immune system homeostasis is vital in the control of human diseases. We have previously demonstrated that the anti-inflammatory cytokine IL-37 participates in immune tolerance by generating semi-mature tolerogenic dendritic cells (DCs) in antigen-specific adaptive immune responses. IL-37 is one of eleven IL-1 family members and the only known member to be broadly anti-inflammatory. In our recent project, we found IL-37 levels were elevated in multiple human immune cell types, specifically in regulatory T (Treg) cells. Our further analysis revealed that human Treg cells express the highest IL-37 levels among all T-cell subsets and that intracellular expression of IL-37 correlates with the expression of master transcriptional regulator, FOXP3, in human Treg cells. Therefore, in the parent grant proposal (R01 AI156534), we hypothesized that the expression of IL-37 upregulates and stabilizes FOXP3, thereby maintaining Treg stability and highly suppressive function in human Treg cells, and we proposed 3 Aims to define transcriptional and translational regulations of IL-37 expression in human Treg cells, molecular mechanisms of IL-37 expression in mediating FOXP3 expression and immune suppression, and the role of IL-37 in human Treg cell heterogeneity. Here, supplemental funding is requested for Dr. Lloyd’s post-doc fellowship to propose an extension to the parent project. The project utilizes human primary Treg cells and various disciplines from immunology, cell biology, molecular biology, and protein chemistry, which would enhance the training of Dr. Lloyd, who has been trained in molecular biology and microbiology. The University of Colorado has a strong Immunology & Microbiology training record, and Dr. Lloyd will have a strong mentor team. Since our proposal uses human T cells, the results could be easily translated into clinical medicine and patient care. The findings will have an immense translational impact on many human diseases, such as autoimmunity and transplantation.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).