Biography:
Ayano Kohlgruber is a Faculty Member within the Division of Immunology at Boston Children’s Hospital. Her primary goal as an immunologist is to investigate the immune-specific basis of human diseases by applying high-throughput molecular, genetic, and immunological assays to decipher immune system specificities and interactions. The Kohlgruber lab combines human and mouse immunology, with single-cell transcriptomics, synthetic biology, and immune-receptor specificity screening approaches to understand the molecular underpinnings of autoimmunity, cancer, and infectious disease. Specifically, the lab aims to understand how T cell tolerance is lost during autoimmune arthritis and what antigens mediate the pathogenic activation of autoinflammatory synovial T cells. Ultimately, she hopes that the antigens identified through her research program can be leveraged to develop precision vaccines and immunotherapeutics that can be curative for patients.
Research Summary:
Rheumatoid arthritis (RA) is a prevalent autoimmune disorder characterized by chronic inflammatory processes that lead to joint destruction. CD4 T cells of the adaptive immune system recognize peptide antigens through their unique T cell receptor and are highly enriched in the inflamed synovium. Interestingly, certain subsets of CD4 T cells are thought to contribute to the inflammation and pathology of the disease by promoting autoantibody responses in patients with RA. However, the identities of the antigens that stimulate CD4 T cells in the joint and how such reactivities relate to the molecular underpinnings of RA pathogenesis have remained elusive. We have developed a method for CD4 T cell antigen discovery in RA that relies on an unbiased genetic screening technology to accurately and comprehensively map synovial T cell specificities. Using this approach, we have identified several autoantigens that have previously never been reported for joint-infiltrating CD4 T cells. The focus of this proposal is to better understand the context by which these self-proteins are recognized by CD4 T cells in the inflamed synovium and develop additional technologies to assess the CD4 T cell specificities against modified proteins that may contribute to autoantibody responses. Knowledge of the self-reactivities of synovial CD4 T cells may help inform the design of future tolerogenic vaccine therapies and thus improve quality of life for patients living with RA.
