Copper Transporter SLC31A1 in Th17 Cells and Multiple Sclerosis

Investigating how copper transport via SLC31A1 regulates pro-inflammatory Th17 cell activity, this project uncovers a novel link between immune cell metabolism and MS, pointing toward new therapeutic targets.
Ongoing Multiple Sclerosis Neurologic Diseases Animal Models Biological & Mechanistic Cytokine Signaling Experimental Platforms & Models Functional Genomics & CRISPR Immunometabolism T Cell Biology Therapeutic Development Translational & Clinical

Funding Year: 2024

Project Overview

Multiple sclerosis (MS) is a chronic autoimmune disease in which immune cells attack the central nervous system, leading to inflammation and neurological damage. T helper 17 (Th17) cells are key drivers of this process, but the molecular mechanisms that regulate their function are not fully understood. This project focuses on SLC31A1, a protein responsible for transporting copper into cells, and investigates how it controls Th17 cell activity. Using a mouse model of MS, researchers examine whether blocking copper uptake by deleting SLC31A1 reduces disease severity. The study also examines how copper influx through SLC31A1 regulates mitochondrial metabolism — including the TCA cycle and OXPHOS — and drives the synthesis of metabolites that epigenetically control gene expression through DNA methylation, providing new mechanistic insight into how Th17 cell function is controlled.

Impact & Innovation

A new metabolic lever in MS.

 

Having established that copper transport via SLC31A1 is essential for Th17 cell function and EAE induction, this project charts a path to suppressing autoimmune brain inflammation at its source — even after disease onset.

  • Demonstrates that SLC31A1 controls Th17 function through mitochondrial metabolism (TCA cycle, OXPHOS) and epigenetic regulation via DNA methylation
  • Lays the foundation for monoclonal antibodies against SLC31A1, with applicability to other Th17-mediated autoimmune diseases
  • Advances the Consortium’s Shared Mechanisms Across Autoimmune Diseases pillar by linking immune cell metabolic regulation to neuroinflammation across autoimmune conditions
Research Approach

A framework designed for discovery

This project combines molecular immunology, metabolic analysis, and animal models to investigate how copper transport regulates autoimmune T cell function. By manipulating SLC31A1 expression and tracking downstream effects on immune cell behavior, the study aims to link cellular metabolism with disease outcomes in multiple sclerosis.

Genetic deletion of SLC31A1 in T cells, combined with experimental autoimmune encephalomyelitis (EAE) mouse models of MS, and molecular and metabolic profiling of Th17 cell function.

Mouse models of MS (EAE), genetically modified T cells lacking SLC31A1, and cellular assays measuring gene expression, metabolic activity (including mitochondrial function), and epigenetic regulation.


Identification of SLC31A1-dependent pathways that drive Th17-mediated inflammation, with the goal of validating copper transport as a therapeutic target. The work supports development of targeted interventions, including monoclonal antibodies, to inhibit SLC31A1 and treat MS and related autoimmune diseases.

Investigators & Institutions

Powering the science

Principal Investigator

Stefan Feske, MD, Colton Consortium Member

Jeffrey Bergstein Professor of Medicine (Department of Pathology); Vice Chair, Research; Director, Ion Channel and Immunity Program, Department of Pathology; Department of Medicine, NYU Grossman School of Medicine, NYU Langone Health

Colton Centers & Institutions

Judith & Stewart Colton Center for Autoimmunity at NYU Langone Health

NYU Grossman School of Medicine

 

Research Outputs

From insight to impact