TAM receptor signaling dictates lesion location and clinical phenotype during experimental autoimmune encephalomyelitis

Ashley Munie Gardner; Jeffrey R Atkinson; Nicole M Wilkinson; Andrew D Jerome; Calli E Bellinger; Andrew R Sas; Benjamin M Segal

doi:10.1016/j.jneuroim.2023.578016

TAM receptor signaling dictates lesion location and clinical phenotype during experimental autoimmune encephalomyelitis

J Neuroimmunol. 2023 Feb 15:375:578016. doi: 10.1016/j.jneuroim.2023.578016. Epub 2023 Jan 20.

Authors

Ashley Munie Gardner¹, Jeffrey R Atkinson², Nicole M Wilkinson³, Andrew D Jerome⁴, Calli E Bellinger⁵, Andrew R Sas⁶, Benjamin M Segal⁷

Affiliations

¹ Department of Neurology, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA; The Neuroscience Research Institute, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA; Graduate Program in Immunology, University of Michigan Medical School, 2978 Taubman Health Sciences Library, 1135 Catherine, Ann Arbor, MI 48109, USA. Electronic address: [email protected].
² Department of Neurology, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA; The Neuroscience Research Institute, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA. Electronic address: [email protected].
³ Department of Neurology, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA. Electronic address: [email protected].
⁴ Department of Neurology, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA; The Neuroscience Research Institute, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA. Electronic address: [email protected].
⁵ Department of Neurology, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA; The Neuroscience Research Institute, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA; Neuroscience Graduate Program, The Ohio State University, 255 Institute for Behavioral Medicine Research Building (IBMR), 460 Medical Center Drive, Columbus, OH 43210, USA. Electronic address: [email protected].
⁶ Department of Neurology, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA; The Neuroscience Research Institute, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA. Electronic address: [email protected].
⁷ Department of Neurology, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA; The Neuroscience Research Institute, The Ohio State University, 395 W. 12th Ave., 7th Floor, Columbus, OH 43210, USA. Electronic address: [email protected].

PMID: 36708633
DOI: 10.1016/j.jneuroim.2023.578016

Abstract

Experimental autoimmune encephalomyelitis (EAE), induced by the adoptive transfer of Th17 cells, typically presents with ascending paralysis and inflammatory demyelination of the spinal cord. Brain white matter is relatively spared. Here we show that treatment of Th17 transfer recipients with a highly selective inhibitor to the TAM family of tyrosine kinase receptors results in ataxia associated with a shift of the inflammatory infiltrate to the hindbrain parenchyma. During homeostasis and preclinical EAE, hindbrain microglia express high levels of the TAM receptor Mer. Our data suggest that constitutive TAM receptor signaling in hindbrain microglia confers region-specific protection against Th17 mediated EAE.

Keywords: Experimental autoimmune encephalomyelitis; Neuroinflammation; TAM receptors.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Encephalomyelitis, Autoimmune, Experimental*
Mice
Mice, Inbred C57BL
Microglia / pathology
Receptor Protein-Tyrosine Kinases
Spinal Cord / pathology

Substances

Receptor Protein-Tyrosine Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding