Role of T-bet in the pathogenesis of experimental autoimmune encephalomyelitis

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Functional experiments using newly generated mouse models revealed that disruption of select ILC-intrinsic pathways significantly attenuated neuroinflammatory responses, suggesting a previously unappreciated contribution of these pathways to disease progression. Additionally, our transcriptomic analyses revealed striking alterations in the metabolic and transcriptional profiles of tissue-resident ILCs during neuroinflammation, pointing to potential shutdown mechanisms or functional reprogramming. These observations led us to hypothesize that specific inflammation-induced ILC states-rather than the tissue-resident populations-may be the primary drivers of CNS autoimmunity. As such, our focus has shifted toward understanding the origin, regulation, and effector programs of these emergent inflammatory ILC states. Together, these studies shed light on a complex and dynamic ILC landscape at the CNS borders and highlight the potential of targeting selective ILC pathways as a means of modulating neuroinflammation without broadly suppressing systemic immunity. Our ongoing work aims to further elucidate how these innate immune cells orchestrate local immune responses and contribute to CNS pathology, with the ultimate goal of identifying tractable therapeutic targets for autoimmune and inflammatory disorders of the brain and spinal cord.