Date of Award

Fall 2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Immunobiology

First Advisor

Medzhitov, Ruslan

Abstract

The immune system has a versatility of functions beyond its response to foreign pathogens. This is the case not only in inflammatory perturbations but in sterile challenges as well. Here we present a role for the family of immune cytokines, type I IFNs, in maintaining homeostasis and mediating adaptation during prolonged food deprivation. We demonstrate that through glucocorticoid mediated upregulation of endogenous retroviral elements (ERVs), cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway is activated and upregulates unique subsets of type I IFNs. These IFNs are necessary for metabolic adaptation that ensures survival of the organism when no food is available. As fasting is typically considered immunosuppressive, we provide a novel example of an inflammatory immune signal acting adaptively in a sterile, non-inflammatory challenge.

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