[R01] The role of GPR132 in regulating T cell responses in infection and cancer
Ente: National Institute of Allergy and Infectious Diseases
Scadenza: 2031-05-31
Importo max: 647.356 EUR
Paese: US
Descrizione
PROJECT SUMMARY.
CD8 T cells play a critical role in protection from a variety of infectious microorganisms, and pathogen-specific
CD8 T cells undergo robust expansion, with an individual T cell clones expanding up to 10,000-fold in a matter
of days. After infection is resolved, the majority of these T cells die, leaving a small population of memory cells
to provide protective immunity from secondary challenge. T cell expansion and contraction are tightly
orchestrated processes that involve a delicate balance between stimulatory and inhibitory signals to ensure
proper immune function. Dysregulation of the T cell response can have detrimental effects; too little proliferation
and the host fails to mount a successful immune response, while excessive proliferation and persistence of
effector T cell populations can lead to tissue damage. This proposal aims to determine the role of the G protein
coupled receptor GPR132 in the regulation of CD8 T cell responses during infection and tumorigenesis. GPR132
detects oxidized endogenous and microbial lipids, and this can lead to cell cycle arrest; however, the role of
GPR132 in CD8 T cells remains unexplored. Here we identify GPR132 as a critical regulator of CD8 T cell
expansion and memory differentiation. Completion of the proposed aims will: 1) uncover the temporal role of
GPR132 in regulating T cell accumulation and function during infection and tumorigenesis, 2) examine the
abundance of GPR132-activating ligands within the tissue during health and disease, and 3) determine how
altering GPR132 ligand availability could be used to enhance/inhibit T cell responses. Overall, these studies will
provide fundamental insights into the regulatory mechanisms that dictate the magnitude of T cell responses and
how they can be modulated therapeutically, which would allow us to boost responses to pathogens/tumors or
inhibit pathogenic responses in the context of autoimmune disease.
Istituzione: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
PI: Tessa Bergsbaken
Progetto: 1R01AI192521-01A1
Settori: National Institute of Allergy and Infectious Diseases
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