Life History of a Brain Autoreactive T Cell: From Thymus Through Intestine to Blood-brain Barrier and Brain Lesion

Overview

Journal Neurotherapeutics

Specialty Neurology

Date 2024 Sep 5

PMID 39237437

Authors

Naoto Kawakami

Hartmut Wekerle

Affiliations

Soon will be listed here.

Abstract

Brain antigen-specific autoreactive T cells seem to play a key role in inducing inflammation in the central nervous system (CNS), a characteristic feature of human multiple sclerosis (MS). These T cells are generated within the thymus, where they escape negative selection and become integrated into the peripheral immune repertoire of immune cells. Typically, these autoreactive T cells rest in the periphery without attacking the CNS. When autoimmune T cells enter gut-associated lymphatic tissue (GALT), they may be stimulated by the microbiota and its metabolites. After activation, the cells migrate into the CNS through the blood‒brain barrier, become reactivated upon interacting with local antigen-presenting cells, and induce inflammatory lesions within the brain parenchyma. This review describes how microbiota influence autoreactive T cells during their life, starting in the thymus, migrating through the periphery and inducing inflammation in their target organ, the CNS.

Citing Articles

Gut microbiota dysbiosis and neurologic diseases: New Horizon with potential diagnostic and therapeutic impact.

Keshavarzian A, Sisodia S Neurotherapeutics. 2024; 21(6):e00478.

PMID: 39488472 PMC: 11585866. DOI: 10.1016/j.neurot.2024.e00478.

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