1. T-bet promotes the accumulation of encephalitogenic Th17 cells in the CNS
- Author
-
Heather M. Grifka-Walk and Benjamin M. Segal
- Subjects
Central Nervous System ,0301 basic medicine ,Encephalomyelitis, Autoimmune, Experimental ,Immunology ,Central nervous system ,Cell ,chemical and pharmacologic phenomena ,Therapeutic targeting ,Article ,Mice ,Mice, Congenic ,03 medical and health sciences ,Chemokine receptor ,medicine ,Demyelinating disease ,Animals ,Immunology and Allergy ,Mice, Knockout ,Chemistry ,Effector ,Cell adhesion molecule ,hemic and immune systems ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Mechanism of action ,Th17 Cells ,Neurology (clinical) ,medicine.symptom ,T-Box Domain Proteins - Abstract
T-bet enhances the encephalitogenicity of myelin-reactive CD4+ T cells, however its mechanism of action is unknown. In this study we show that T-bet confers a competitive advantage for the accumulation of IL-23 conditioned Th17 effector cells in the central nervous system (CNS). Impaired migration of T-bet deficient Th17 cells to the CNS is associated with altered expression of adhesion molecules and chemokine receptors on their cell surface. Our data suggest that therapeutic targeting of T-bet in individuals with Th17-mediated autoimmune demyelinating disease may inhibit inflammatory infiltration of the CNS and, hence, clinical exacerbations.
- Published
- 2017
- Full Text
- View/download PDF