Stopping T cells entering the brain in MS

Dr Iain Comerford

University of Adelaide

| Better treatments | Immunology | Fellowship | 2022 | Investigator Led Research |
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Summary

In MS, cells of the immune system enter the brain and spinal cord and produce substances that cause inflammation, resulting in damage that leads to the disease symptoms. Understanding how the immune cells enter the brain is likely to lead to better therapeutics that can interfere with this process.

This project will focus on the ways in which inflammatory immune cells called T cells, enter the brain. New ways to block inflammatory T cell migration will be tested and the disease-causing T cells will be examined in more detail in this study.

This project should identify new ways in which MS may be better treated in the future.

Progress to Date

Dr Iain Comerford and his team have achieved significant progress across various projects exploring how immune cells causing inflammation, infiltrate the brain in models of MS. Investigating the impact of a receptor (protein found on the surface or within cells that interact with other molecules) called CXCR6 on inflammatory cell migration laid the foundation for a manuscript. The team are currently exploring further into CXCR6 and the collective role of other chemokine receptors in this migration.

Another focus involved studying RUNX2 in T cells within MS models. RUNX2 is a protein that is involved in regulating the levels of genes. The findings highlighted that T cells lacking RUNX2 display heightened sensitivity to stimulation, unveiling new insights of T cell activation regulation relative to MS.

Cutting-edge next-generation sequencing was initiated to comprehensively map the array of receptors controlling T cell migration in the brains of MS laboratory models. This data will provide a detailed understanding of migrating T cell types and the receptor combinations they carry.

Further achievements include publications in reputable journals, securing more funding to extend the research, and mentoring exceptional students. The team has delivered presentations at the Australian and New Zealand Society for Immunology (ASI) Adelaide Immunology Retreat and other eminent conferences showcasing work from this fellowship.

The dedication from Dr Comerford and his team promises rich insights into immune responses associated with MS.

Publications

  • Heng AHS, Han CW, Abbott C, McColl SR and Comerford I. Chemokine-driven migration of pro-inflammatory CD4+ T cells in CNS autoimmune disease. Frontiers in Immunology. 2022. 13:817473
  • Bastow CR, Kara EE, Tyllis TS, Vinuesa CG, McColl SR and Comerford I. Tfr cells express functional CCR6 but it is dispensable for their development and localisation during splenic humoral immune responses. Frontiers in Immunology. 2022. 13:873586
  • Foeng J, Comerford I and McColl SR. Harnessing the chemokine system to home CAR-T cells into solid tumours. Cell Reports Medicine. 2022. 3(3):100543 Nheu D, Ellen O, Ye S, Ozturk E, Pagnin M, Kertadjaja S, Theotokis P, Grigoriadis N, McLean C, Petratos S. (2022) Modulation of the Microglial Nogo-A/NgR Signaling Pathway as a Therapeutic Target for Multiple Sclerosis. Cells. 11(23):3768

Updated: 31 March 2023

Updated: 14 February, 2022

Stages of the research process

Fundamental laboratory
Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline: 10+ years
Translational
Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline: 5+ years
Clinical Studies
and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline: 1-5 years

Investigator

Grant Awarded

  • Fellowship Grant

Total Funding

  • $390,000

Duration

  • 3 years

Funding Partner

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Stopping T cells entering the brain in MS